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Congestive Heart Failure

1. Arzneimittelforschung. 1993 Mar;43(3):308-12. (Animal Study)

Effects on heart membranes after taurine treatment in rabbits with congestive heart failure.

Elizarova EP, Orlova TR, Medvedeva NV.

Russian Academy of Medical Science, Cardiology Research Center, Moscow.

Oral treatment with taurine (CAS 107-35-7) of rabbits with congestive heart failure (CHF) caused by impairment of aortic valve dose-dependently improved hemodynamic and contractile indices of the heart and prolonged the animals' life. Analysis of heart membrane fraction of CHF animals, using a paramagnetic probe 4-tempo-stearamide, demonstrated a loss of negative charge of the membranes. In vitro addition of taurine had no effect on the charge of phospholipid heads. The use of a 5-doxyl-stearate probe revealed that membrane fluidity decreased with the development of CHF as compared with normal membranes. Taurine increased membrane fluidity in animals with CHF, but did not affect membranes isolated from animals with CHF which had undergone taurine treatment and elevated membrane rigidity in the control group.

2. Jpn Circ J. 1992 Jan;56(1):95-9.

Usefulness of taurine in chronic congestive heart failure and its prospective application.

Azuma J, Sawamura A, Awata N.

Third Department of Internal Medicine, Osaka University Medical School, Japan.

We compared the effect of oral administration of taurine (3 g/day) and coenzyme Q10 (CoQ10) (30 mg/day) in 17 patients with congestive heart failure secondary to ischemic or idiopathic dilated cardiomyopathy, whose ejection fraction assessed by echocardiography was less than 50%. The changes in echocardiographic parameters produced by 6 weeks of treatment were evaluated in a double-blind fashion. In the taurine-treated group significant treatment effect was observed on systolic left ventricular function after 6 weeks. Such an effect was not observed in the CoQ10-treated group.

3. Kardiologiia. 1991 Jun;31(6):77-80. (Animal Study)

[Use of taurine in the treatment of experimental congestive heart failure]

[Article in Russian]

Orlova TsR, Elizarova EP, Ryff IM, Fetisova NI, Mit'kina LI.

The therapeutic effects of 2-aminoethanesulfonic acid (taurine) were tested in animals with congestive heart failure (HF) simulated by aortic valve damage. The drug given in a daily dose of 100 mg/kg for a month was shown to reduce mortality rates as compared to controls, to improve the animals' clinical condition, hemodynamic and myocardial contractility parameters. Taurine was found to exert a positive action on the heart response to stresses. The impaired response in the animals restored to heart rate stimulation, catecholamines and calcium loading. The mechanisms of the agent's action are discussed in the present paper. It is suggested that taurine-based taucard will be included into the arsenal of cardiotropic agents after its clinical trials are successfully completed.

4. Am Heart J. 1986 Dec;112(6):1278-84. (Animal Study)

Beneficial effect of taurine in rabbits with chronic congestive heart failure.

Takihara K, Azuma J, Awata N, Ohta H, Hamaguchi T, Sawamura A, Tanaka Y, Kishimoto S, Sperelakis N.

To examine the effect of daily treatment with taurine on improving the status of congestive heart failure (CHF), we used rabbits with artificially induced aortic regurgitation. Ten rabbits were treated daily with taurine (100 mg/kg by mouth) and eight with guanidinoethyl sulfonate (GES) (100 mg/kg by mouth) immediately after induction of aortic regurgitation. The cumulative mortality rate at 8 weeks in the taurine-treated CHF group was 10% (1 of 10) compared with 53% (16 of 30) in the nontreated CHF group and 75% (6 of 8) in the GES-treated CHF group (p less than 0.05). Although cardiac function (max dP/dt) in CHF rabbits was significantly decreased (p less than 0.001), taurine-treated CHF rabbits maintained the same values as control rabbits. Taurine content of the left ventricular tissue of the CHF rabbits was significantly increased (p less than 0.01). Administration of taurine and GES to control rabbits for 8 weeks affected neither the hemodynamics nor the taurine content of the heart. It was concluded that taurine slowed the rapid progression of heart failure and consequently prolonged life expectancy.

5. Clin Cardiol. 1985 May;8(5):276-82.

Therapeutic effect of taurine in congestive heart failure: a double-blind crossover trial.

Azuma J, Sawamura A, Awata N, Ohta H, Hamaguchi T, Harada H, Takihara K, Hasegawa H, Yamagami T, Ishiyama T, et al.

In a double-blind, randomized, crossover, placebo-controlled study, we investigated the effects of adding taurine to the conventional treatment in 14 patients with congestive heart failure for a 4-week period. Compared with placebo, taurine significantly improved the New York Heart Association functional class (p less than 0.02), pulmonary crackles (p less than 0.02), and chest film abnormalities (p less than 0.01). A benefit of taurine over placebo was demonstrated when an overall treatment response for each patient was evaluated on the basis of clinical examination (p less than 0.05). No patient worsened during taurine administration, but four patients did during placebo. Pre-ejection period (corrected for heart rate) decreased from 148 +/- 14 ms before taurine treatment to 137 +/- 12 ms after taurine (p less than 0.001), and the quotient pre-ejection period/left ventricular ejection time decreased from 47 +/- 9 to 42 +/- 8% (p less than 0.001). Side effects did not occur in the patients during taurine. The results indicate that addition of taurine to conventional therapy is safe and effective for the treatment of patients with congestive heart failure.

6. Res Commun Chem Pathol Pharmacol. 1984 Aug;45(2):261-70. (Animal Study)

Beneficial effect of taurine on congestive heart failure induced by chronic aortic regurgitation in rabbits.

Azuma J, Takihara K, Awata N, Ohta H, Sawamura A, Harada H, Kishimoto S.

Taurine (2-aminoethanesulfonic acid) is known to have a cardiotonic action. The present study was designed to see whether oral treatment with taurine could improve the status of congestive heart failure induced by aortic regurgitation. Nine rabbits were treated daily with taurine (100 mg/kg) after producing aortic regurgitation. Cumulative mortality at 8 weeks in the non-treated group was 52% compared with 11% in the taurine-treated group (p less than 0.05). Cardiac function (max dP/dt) was significantly decreased in rabbits with aortic regurgitation, whereas in taurine-treated rabbits, cardiac function was maintained the same as control. The present data suggest that taurine prevented the rapid progress of heart failure, and consequently prolonged the life expectancy.

7. Clin Ther. 1983;5(4):398-408.

Therapy of congestive heart failure with orally administered taurine.

Azuma J, Hasegawa H, Sawamura A, Awata N, Ogura K, Harada H, Yamamura Y, Kishimoto S.

The clinical efficacy of 2 gm BID of oral taurine (2-aminoethane sulfonic acid) was studied in 24 patients with congestive heart failure (CHF). We expressed the severity of CHF by a score based on clinical signs and symptoms and on roentgenographic data. The maximum possible score, corresponding to the worst CHF, was 23 points. How much the 24 patients improved after receiving taurine for four or eight weeks was estimated by the difference between their pretreatment and posttreatment scores. In 19 of the 24 patients, taurine was effective. In the group as a whole, mean (+/- SEM) scores fell significantly, from 7.3 +/- 0.6 before treatment to 4.4 +/- 0.5 after treatment. Thirteen of the 15 patients who were designated as New York Heart Association (NYHA) functional class III or IV before receiving taurine could be designated as class II after they completed the study. This pilot study should prompt further investigation into the possible use of taurine in the treatment of patients with CHF.

8. Physiol Chem Phys. 1977;9(3):259-63. (Animal Study)

A relation between myocardial taurine contest and pulmonary wedge pressure in dogs with heart failure.

Newman WH, Frangakis CJ, Grosso DS, Bressler R.

Myocardial taurine levels were correlated with pulmonary wedge pressure (PWP) in dogs with congestive heart failure (CHF). Heart failure was induced by creating an infrarenal aortocaval fistula. PWP ranged from 6.6 to 28 mm Hg, suggesting a wide range in severity of heart failure in those dogs. Compared to taurine levels of normal dogs, levels of the CHF group were significantly elevated in both left and right ventricles. Linear regression analysis of ventricular taurine content yielded a highly significant direct relation to PWP. The results suggest that myocardial taurine content increases as heart failure becomes more severe.

Hypertension

9. Amino Acids. 2002;23(4):381-93.

Treatment of hypertension with oral taurine: experimental and clinical studies.

Militante JD, Lombardini JB.

Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA.

Oral taurine treatment has been studied extensively as a hypotensive agent. Several rat models of hypertension have been used to prove that dietary taurine supplementation can alleviate high blood pressure, among other cardiovascular problems. Experimental models mentioned in this review are the spontaneously hypertensive rat, the DOCA-salt rat, the Dahl-S rat, the renovascular hypertensive rat, the hyperinsulinemic rat and the ethanol-treated rat. The beneficial effects of taurine were also demonstrated in studies involving human subjects suffering essential hypertension. Taurine supplementation of 6 g/day for as little as 7 days resulted in measurable decreases in blood pressure in these patients. In both rat and human studies, the effects of taurine appeared to be dependent on the modulation of an overactive sympathetic system. However, taurine has positive effects on other types of cardiovascular problems and thus may act through more than one mechanism.

10. Poult Sci. 2001 Nov;80(11):1607-18. (Animal Study)

Taurine, cardiopulmonary hemodynamics, and pulmonary hypertension syndrome in broilers.

Ruiz-Feria CA, Wideman RF Jr.

Department of Poultry Science, University of Arkansas, Fayetteville 72701, USA. cruizfe@hotmail.com

Previous studies have suggested cardiac taurine is released into the plasma in response to hypoxemia (low blood oxygen levels) during the pathogenesis of pulmonary hypertension syndrome (PHS, ascites). In the present study, broilers reared under cool temperature conditions (16 C) were provided tap water (control group), tap water supplemented with taurine, or tap water supplemented with the taurine transport antagonist beta-alanine. When compared with control values, taurine supplementation consistently elevated free taurine concentrations in the plasma but not in cardiac tissues, whereas beta-alanine supplementation consistently reduced free taurine concentrations in cardiac tissues but not in the plasma. Neither the incidence of PHS nor specific predictors of PHS susceptibility (electrocardiogram Lead II S-wave amplitude, % saturation of hemoglobin with oxygen, heart rate, right to total ventricular weight ratio) were affected by taurine or beta-alanine supplementation. Cardiopulmonary hemodynamic evaluations were conducted to compare control and beta-alanine supplemented broilers breathing room air or air containing 12% oxygen (low oxygen challenge). While breathing room air, the betaalanine-supplemented broilers had higher baseline values for cardiac output (186.2 vs. 146.9 mL/min/kg BW) and pulmonary arterial pressure (27.4 vs. 22.4 mm Hg), similar values for mean systemic arterial pressure (100 vs. 104 mm Hg) and pulmonary vascular resistance (0.062 vs. 0.064 resistance units), and lower values for total peripheral resistance (0.228 vs. 0.296 resistance units) when compared with control broilers breathing room air. During low oxygen challenges, the beta-alanine-supplemented broilers exhibited larger reductions in cardiac output, mean systemic arterial pressure, and pulmonary arterial pressure and greater increases in pulmonary vascular resistance than control broilers. These observations indicate that beta-alanine-supplemented broilers breathing room air had a higher systemic demand for oxygen as evidenced by their lower total peripheral resistance (systemic vasodilation) and had a capacity sufficient to pump a higher cardiac output and, thereby, maintain a similar mean systemic arterial pressure when compared with control broilers. However, cardiac function rapidly deteriorated in beta-alanine-supplemented broilers during low oxygen challenges, leading to substantially greater reductions in cardiac output, stroke volume, and mean systemic arterial pressure when compared with control broilers. Concurrent changes in pulmonary arterial pressure within the beta-alanine group reflect interactions between cardiac output and pulmonary vascular resistance. Overall, depleting cardiac taurine did not appear to initiate PHS, but systemic hypoxemia developing during the mid- to late-pathogenesis of PHS may expose and incipient cardiac weakness attributable to depleted taurine reserves.

11. Amino Acids. 2000;19(3-4):643-65. (Animal Study)

Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat.

Dawson R Jr, Liu S, Jung B, Messina S, Eppler B.

Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610, USA. dawson@cop.health.ufl.edu

Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms. The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water (n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets. High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes (Na+, K+), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (microg/24h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects in SPSHR given high salt diets.

12. Amino Acids. 2000;19(3-4):643-65. (Animal Study)

Effects of high salt diets and taurine on the development of hypertension in the stroke-prone spontaneously hypertensive rat.

Dawson R Jr, Liu S, Jung B, Messina S, Eppler B.

Department of Pharmacodynamics, College of Pharmacy, University of Florida, Gainesville 32610, USA. dawson@cop.health.ufl.edu

Taurine is present in high concentrations in mammalian tissues and has been implicated in cardiovascular control mechanisms. The aim of the present study was to evaluate the ability of taurine to attenuate salt-induced elevations in blood pressure and markers of damage to the kidney and cardiovascular system in stroke prone spontaneously hypertensive rats (SPSHR). Male SPSHR (6 weeks old) were placed on high salt diets that contained 1% (w/w) NaCl added to their normal chow for 84 days and then were switched to 3% added NaCl for the remaining 63 days of the study. SPSHR was given 1.5% taurine in the drinking water (n = 8), a taurine free diet (n = 8) or normal chow (n = 8). A final control group (n = 6) was not given high salt diets. High salt diets caused an acceleration in the development of hypertension in all groups. Taurine supplementation reduced ventricular hypertrophy and decreased urinary excretion of protein and creatinine. The taurine free diet did not alter serum or urinary excretion of taurine, but did result in elevated urinary nitrogen excretion, increased serum cholesterol levels, and impaired performance in a spatial learning task. Alterations in dietary taurine intake did not alter urinary or serum electrolytes (Na+, K+), but taurine supplementation did attenuate a rise in serum calcium seen with the high salt diets. Urinary excretion (microg/24h) of epinephrine and dopamine was significantly reduced in SPSHR given 1% NaCl in the diet, but this effect was not seen in SPSHR on taurine free or supplemented diets. Taurine supplementation showed cardioprotective and renoprotective effects in SPSHR given high salt diets.

13. Hypertens Res. 2000 May;23(3):277-84.

Oral taurine supplementation prevents the development of ethanol-induced hypertension in rats.

Harada H, Kitazaki K, Tsujino T, Watari Y, Iwata S, Nonaka H, Hayashi T, Takeshita T, Morimoto K, Yokoyama M.

First Department of Internal Medicine, Kobe University School of Medicine, Japan.

Taurine is known to lower blood pressure in essential hypertension and some experimental hypertensive models. Taurine has also been reported to activate aldehyde dehydrogenase and to inhibit the elevation of plasma acetaldehyde concentration after ethanol intake. Because acetaldehyde, the first metabolite of ethanol, is suspected to be responsible for many adverse effects of alcohol consumption, we examined the effect of taurine supplementation on ethanol-induced hypertension and abnormalities in the intracellular cation metabolism in Witar-Kyoto rats. In Study 1, systolic blood pressure and intraplatelet free calcium were significantly higher in rats who received 15% ethanol in drinking water than in control rats. Oral taurine supplementation (1% taurine and 15% ethanol in drinking water) completely prevented the development of ethanol-induced hypertension. Intraerythrocyte sodium and intraplatelet free calcium were significantly decreased in taurine-supplemented rats as compared with rats who received 15% ethanol only. In Study 2, hemoglobin-associated acetaldehyde (HbAA) was measured as a marker of protein-bound acetaldehyde. HbAA was significantly elevated in rats who received 5% ethanol in drinking water as compared with control rats. Taurine supplementation (1% taurine and 5% ethanol in drinking water) significantly decreased HbAA. Our findings suggest that the oral supplementation of taurine prevents ethanol-induced hypertension by decreasing protein bound acetaldehyde and altering the cation handling by the membrane.

14. Can J Physiol Pharmacol. 1999 Oct;77(10):749-54. (Animal Study)

Taurine attenuates hypertension and improves insulin sensitivity in the fructose-fed rat, an animal model of insulin resistance.

Anuradha CV, Balakrishnan SD.

Department of Biochemistry, Annamalai University, Annamalai Nagar, Tamil Nadu, India.

Fructose feeding induces moderate increases in blood pressure levels in normal rats, which is associated with hyperinsulinemia, insulin resistance, and impaired glucose tolerance. Increased vascular resistance, sodium retention, and sympathetic overactivity have been proposed to contribute to the blood pressure elevation in this model. Taurine, a sulphur-containing amino acid, has been reported to have antihypertensive and sympatholytic actions. In the present study, the effects of taurine on blood pressure, plasma levels of glucose and insulin, glucose tolerance, and renal function were studied in fructose-fed rats. Fructose-fed rats had higher blood pressure and elevated plasma levels of insulin and glucose. The plasma glucose levels were higher in fructose-fed rats than in controls at 15, 30, and 60 min after the oral glucose load. Treatment with 2% taurine in drinking water prevented the blood pressure elevation and attenuated the hyperinsulinemia in fructose-fed rats. The exaggerated glucose levels in response to the oral glucose load was also prevented by taurine administration. Thus, taurine supplementation could be beneficial in circumventing metabolic alterations in insulin resistance.

15. Poult Sci. 1999 Nov;78(11):1627-33. (Animal Study)

Plasma taurine levels in broilers with pulmonary hypertension syndrome induced by unilateral pulmonary artery occlusion.

Ruiz-Feria CA, Beers KW, Kidd MT, Wideman RF Jr.

Department of Poultry Science, University of Arkansas, Fayetteville 72701, USA. cruizfe@comp.uark.edu

Low plasma levels of taurine are associated with losses of cardiac sarcomeric proteins, leading to heart failure in mammals. Recently, it was proposed that cardiac taurine depletion serves to defend the heart against injury caused by regional ischemia in mammals. The role of taurine has not been well documented in broilers, particularly in relation to pulmonary hypertension syndrome (PHS; ascites). Three independent experiments evaluated plasma taurine in male broilers by utilizing the following treatments: unoperated controls (CONTROL; n = 10 in each experiment); sham operated (SHAM; n = 11, 12, and 10); or, unilaterally pulmonary artery clamped (PAC; n = 18, 29, and 24) that did (PAC-ascites) or did not (PAC-normal) develop ascites within 12 d postsurgery. Plasma samples were collected 9 and 11 d postsurgery in Experiments 1 and 2, respectively, and 2 d before and 4, 8, and 12 d after surgery in Experiment 3. Plasma taurine was analyzed by HPLC. Twelve days postsurgery, the birds were euthanatized, and ventricles were weighed for calculating the right:total ventricular weight ratio (RV:TV). The RV:TV of PAC birds (>0.35) consistently was higher (P < 0.01) than that of CONTROL and SHAM birds (<0.27 and 0.25, respectively). In Experiments 1 and 2, plasma taurine was higher (P < 0.05) in PAC-ascites (380 and 370 nmol/mL) than in SHAM broilers (183 and 186 nmol/mL), whereas CONTROL (262 and 278 nmol/mL) and PAC-normal (362 and 300 nmol/mL) broilers tended to have intermediate plasma taurine levels. In Experiment 3, PAC birds had higher (P < 0.05) plasma taurine at 8 and 12 d postsurgery when compared with presurgery levels, whereas plasma taurine was unchanged over time in CONTROL and SHAM birds. These results suggest cardiac taurine may be released into the plasma as a protective mechanism in response to the induction of pulmonary hypertension, hypoxemia, and right-side heart failure, similar to the mechanism reported for protecting cardiac muscle from ischemia in mammals.

16. J Hypertens. 1994 Jun;12(6):653-61. (Animal Study)

Taurine amplifies renal kallikrein and prevents salt-induced hypertension in Dahl rats.

Ideishi M, Miura S, Sakai T, Sasaguri M, Misumi Y, Arakawa K.

Department of Internal Medicine, Fukuoka University School of Medicine, Japan.

OBJECTIVE: To determine whether taurine reduces blood pressure by stimulating the renal kallikrein-kinin system. METHODS: The effects of taurine on blood pressure, urinary kallikrein activity and renal kallikrein gene expression were investigated in Dahl salt-sensitive (Dahl-S) rats. The specificity of the action of taurine was verified by comparison with the action of beta-alanine, a carboxylic analogue of taurine. The effect of co-administration of the specific bradykinin B2 receptor antagonist Hoe 140 was also examined. RESULTS: Administration of taurine (3% in drinking water) for 4 weeks retarded the development of salt (4% sodium chloride diet)-induced hypertension. Systolic blood pressure at the end of the experiment was significantly higher in control rats than in taurine-treated rats. Urinary sodium excretion was not decreased by the reduction in blood pressure. The heart weight:body weight ratio was significantly lower, and urinary volume and kallikrein excretion were significantly higher, in taurine-treated rats. Renal kallikrein gene expression at weeks 1 and 4 was higher in taurine-treated rats. Systolic blood pressure 3 and 4 weeks after the administration of beta-alanine was slightly, but not significantly, lower than that of untreated rats on a high-salt diet, and was accompanied by a significantly lower body weight. Urinary kallikrein excretion decreased with a high-salt diet regardless of beta-alanine administration. Continuous systemic administration of Hoe 140 did not cause any significant alteration in blood pressure in Dahl-S rats that received taurine with a high-salt diet. Taurine also showed a renoprotective effect, as judged by a reduction in proteinuria. CONCLUSION: These results suggest that taurine is an effective antihypertensive agent for salt-induced hypertension. Although taurine activated renal kallikrein, further studies are required to confirm the participation of activated kallikrein in the antihypertensive, cardioprotective and renoprotective effects of taurine.

17. Cardiovasc Res. 1988 May;22(5):351-8. (Animal Study)

Retardation of the development of hypertension in DOCA salt rats by taurine supplement.

Inoue A, Takahashi H, Lee LC, Sasaki S, Kohno Y, Takeda K, Yoshimura M, Nakagawa M.

2nd Department of Medicine, Kyoto Prefectural University of Medicine, Japan.

To study the antihypertensive effect of orally administered taurine in DOCA salt hypertension, urinary excretion of catecholamines, electrolytes, and arg-vasopressin was measured over four weeks in 20 taurine treated DOCA rats (group 1), 20 taurine untreated DOCA rats (group 2), and seven taurine untreated sham operated rats (group 3). Additional experiments were performed to determine whether or not the pressor and sympathetic responses to hypothalamic stimulation were altered after taurine treatment in DOCA rats. Systolic blood pressure decreased significantly in group 1 after the first week compared with that in group 2, and the differences became progressively more evident thereafter. At the fifth week the mean blood pressure was significantly lower in group 1 than in group 2, as was the heart rate. Although urinary excretion of adrenaline decreased significantly in group 1 at the first and fourth weeks, the difference in urinary excretion of noradrenaline between groups 1 and 2 was not significant. Urinary excretion of adrenaline and noradrenaline in group 3 was significantly lower than that in both hypertensive groups (groups 1 and 2). Urinary sodium excretion increased significantly in group 1 at the first and second week compared with group 2. With graded electrical stimulation of the ventromedial hypothalamus, resulting pressor and sympathetic responses were significantly smaller in group 1 than in group 2. These results suggest that the hypotensive effects of orally administered taurine in DOCA hypertensive rats are caused by suppression of the peripheral sympathetic nervous activity and by the resulting natriuresis.

18. Hypertension. 1987 Oct;10(4):383-9.

Inhibition of hypertension and salt intake by oral taurine treatment in hypertensive rats.

Abe M, Shibata K, Matsuda T, Furukawa T.

Department of Pharmacology, School of Medicine, Fukuoka University, Japan.

Effects of oral treatment with taurine on fluid intakes produced by renin were assessed in spontaneously hypertensive rats of the Okamoto strain (SHR). Renin injected into the preoptic area increased water intake and evoked salt (2.7% NaCl solution) intake, and angiotensin II injected into this area increased water intake, but not salt intake, in both SHR and control normotensive Wistar-Kyoto rats (WKY). The salt intake elicited by renin, but not water intake produced by renin or angiotensin II, was potentiated in SHR. These effects of renin and angiotensin II on fluid intakes were antagonized by previous administration of taurine or gamma-aminobutyric acid into the cerebral ventricles in both strains. When SHR received water containing 3% taurine from 32 to 105 days of age, development of hypertension was inhibited. Renin administered into the preoptic area at 105 days of age caused an increase in salt intake, but the increase was markedly inhibited by the oral administration of taurine as well. These results show that salt appetite produced by centrally administered renin is exaggerated in SHR and that development of hypertension as well as renin-induced salt appetite in SHR is inhibited by dietary taurine.

19. Jpn Heart J. 1983 Jan;24(1):91-102.

Decrease of urinary taurine in essential hypertension.

Kohashi N, Katori R.

In order to evaluate how taurine relates to the pathogenesis of essential hypertension, the taurine content of plasma, whole blood and urine was measured in 18 normals and in 79 hypertensive patients. The patients included 32 untreated cases of essential hypertension, 32 treated cases and 15 cases with labile hypertension. There were no statistically significant differences between normals and essential hypertensives in either plasma or whole blood taurine content. However, in comparison to urinary taurine excretion in normals, 1594.0 +/- 143.7 mumol/day (mean +/- SE), that for untreated essential hypertensives, 708.1 +/- 57.1 mumol/day (p less than 0.001), and for treated essential hypertensives, 953.6 +/- 94.3 mumol/day (p less than 0.001), were significantly lower. Those with labile hypertension showed almost the same value, 1478.3 +/- 134.3 mumol/day, as normals. Taurine clearance and the taurine/creatinine ratio were also markedly decreased in essential hypertensives without treatment. For all subjects, taurine clearance had a positive correlation (r = 0.327, p less than 0.01) with creatinine clearance, but there were significant negative correlations between systolic blood pressure and daily urinary taurine excretion (r = -0.472, p less than 0.01) and between diastolic blood pressure and daily urinary taurine excretion (r = -0.382, p less than 0.01). There were also significant positive correlations between daily urinary taurine excretion and serum high-density lipoprotein cholesterol (r = 0.559, p less than 0.01) and between the former and cardiac index (r = 0.547, p less than 0.01). These results suggest that a deficiency of taurine plays an important role not only in elevating blood pressure in essential hypertension but also in atherogenesis as well.

Glucose Metabolism

20. Amino Acids. 2002;22(1):27-38.

Taurine modulates kallikrein activity and glucose metabolism in insulin resistant rats.

Nandhini AT, Anuradha CV.

Department of Biochemistry, Faculty of Science, Annamalai University, Tamil Nadu, India.

Taurine, a potent antioxidant has been reported to show an anti-diabetic effect in streptozotocin-induced diabetes mellitus in which the development of hyperglycemia results from the damage to beta cells of pancreas by reactive oxygen species. In addition, taurine also increases the excretion of nitrite and enhances the formation of kinins and would be expected to improve insulin resistance. The effect of taurine on insulin sensitivity was examined in the high fructose-fed rats, an animal model of insulin resistance. Male Wistar rats of body weight 170-190g were divided into 4 groups: a control group and taurine-supplemented control group, taurine supplemented and unsupplemented fructose-fed group. An intravenous glucose tolerance test (IVGTT) and a steady state plasma glucose level (SSPG) were performed before the sacrifice. The fructose-fed rats displayed hyperglycemia and insulin resistance and they had a greater accumulation of glycogen than did control rats. Hyperglycemia and insulin resistance were significantly lower in the taurine supplemented fructose-fed group than in the unsupplemented fructose-fed group. Urinary kallikrein activity was higher in taurine-treated animals than in the rats fed only fructose. The activity of membrane bound ATPases were significantly lower in fructose-fed rats than in the control rats and were significantly higher in the taurine supplemented group than in the fructose-fed group. Taurine effectively improves glucose metabolism in fructose-fed rats presumably via improved insulin action and glucose tolerance.

Membrane Protection

21. Drug Chem Toxicol. 2001 Nov;24(4):429-37.

Protective role of vitamin E, 2-deoxy-D-glucose, and taurine on perchloroethylene induced alterations in ATPases.

Ebrahim AS, Babu E, Thirunavukkarasu C, Sakthisekaran D.

Department of Medical Biochemistry, Dr. ALM Post-Graduate Institute of Basic Medical Sciences, University of Madras, Taramani, Chennai 600113, India.

Perchloroethylene (PER) administered by oral gavage for 15 consecutive days, at a dose of 3000 mg/kg body wt. decreased the activities of Na+, K(+)-ATPase and Mg(2+)-ATPase with an increase in the activity of Ca(2+)-ATPase. It also decreased RBC and platelet counts but the WBC count was found to be increased. An investigation of the relative importance of the modulators, vitamin E, 2-deoxy-D-glucose (2DG) and taurine in rendering protection to tissues against PER induced membrane damage was performed. PER administered mice were subjected to vitamin E (400 mg/kg body wt/day), 2DG (500 mg/kg body wt/day by i.p.) and taurine (100 mg/kg body wt/day) administration for 15 days to study their individual effect on ATPase and on certain hematological parameters. Vitamin E, 2DG and taurine treated mice showed a marked reversal of these metabolic changes related to membrane damage caused by PER. These results suggest that PER induced membrane damage may be associated with energy metabolism and hemolysis, which can be effectively prevented by these modulators.

Diabetes

22. Diabetes. 2003 Feb;52(2):499-505. (Animal Study)

Comparative trial of N-acetyl-cysteine, taurine, and oxerutin on skin and kidney damage in long-term experimental diabetes.

Odetti P, Pesce C, Traverso N, Menini S, Maineri EP, Cosso L, Valentini S, Patriarca S, Cottalasso D, Marinari UM, Pronzato MA.

Department of Internal Medicine, University of Genova, Italy.

This study analyzes the effect of chronic treatment with different antioxidants (N-acetyl-cysteine [NAC], taurine, a combination of NAC and taurine, and oxerutin) on long-term experimental diabetes induced by streptozotocin in rats. Glycoxidative damage was evaluated in the skin; glomerular structural changes were studied with morphometry and immunohistochemistry. Oxerutin treatment and the combined NAC plus taurine treatment resulted in reduced accumulation of collagen-linked fluorescence in skin in comparison with untreated diabetic rats. All treatments except taurine reduced glomerular accumulation of N(epsilon)-(carboxymethyl)lysine and protected against the increase in glomerular volume typical of diabetes; furthermore, the apoptosis rate was significantly decreased and the glomerular cell density was better preserved. Glycoxidative markers in the skin turned out to be good indicators of the glomerular condition. The findings that emerged from our study support the hypothesis that glomerular damage in diabetes can be prevented or at least attenuated by supplementation with specific antioxidants. Treatment with oxerutin and combined treatment with NAC plus taurine gave the most encouraging results, whereas the results of taurine-only treatment were either negligible or negative and therefore suggest caution in the use of this molecule in single-drug treatment courses.

23. Diabetes Metab Res Rev. 2001 Sep-Oct;17(5):330-46.

The role of taurine in diabetes and the development of diabetic complications.

Hansen SH.

Department of Clinical Biochemistry, Rigshospitalet, Copenhagen University Hospital, Denmark. shhansen@rh.dk

The ubiquitously found beta-amino acid taurine has several physiological functions, e.g. in bile acid formation, as an osmolyte by cell volume regulation, in the heart, in the retina, in the formation of N-chlorotaurine by reaction with hypochlorous acid in leucocytes, and possibly for intracellular scavenging of carbonyl groups. Some animals, such as the cat and the C57BL/6 mouse, have disturbances in taurine homeostasis. The C57BL/6 mouse strain is widely used in diabetic and atherosclerotic animal models. In diabetes, the high extracellular levels of glucose disturb the cellular osmoregulation and sorbitol is formed intracellularly due to the intracellular polyol pathway, which is suspected to be one of the key processes in the development of diabetic late complications and associated cellular dysfunctions. Intracellular accumulation of sorbitol is most likely to cause depletion of other intracellular compounds including osmolytes such as myo-inositol and taurine. When considering the clinical complications in diabetes, several links can be established between altered taurine metabolism and the development of cellular dysfunctions in diabetes which cause the clinical complications observed in diabetes, e.g. retinopathy, neuropathy, nephropathy, cardiomyopathy, platelet aggregation, endothelial dysfunction and atherosclerosis. Possible therapeutic perspectives could be a supplementation with taurine and other osmolytes and low-molecular compounds, perhaps in a combinational therapy with aldose reductase inhibitors. Copyright 2001 John Wiley & Sons, Ltd.

24. Cardiovasc Res. 2000 Jun;46(3):393-402.

The role of taurine in the pathogenesis of the cardiomyopathy of insulin-dependent diabetes mellitus.

Militante JD, Lombardini JB, Schaffer SW.

Department of Pharmacology, Texas Tech University, Health Sciences Center, Lubbock 79430, USA.

The cellular and molecular physiology and pathology of insulin-dependent diabetes mellitus (IDDM) and non-insulin-dependent diabetes mellitus (NIDDM) are mostly studied and understood through the use of animal models. Fundamental differences between the IDDM and NIDDM animal models may help to explain the etiology behind diabetic cardiomyopathy, one of the most severe complications of IDDM. Experimental rat models of IDDM exhibit a characteristic increase in tissue levels of taurine in the heart, a change that is not seen in NIDDM rats. This article deals with the causes and possible consequences of this observation which may contribute to the development of diabetic cardiomyopathy. Modulation of pyruvate dehydrogenase (lipoamide) (PDH; EC 1.2.4.1) activity was found to be a possible mode for taurine involvement. PDH is a mitochondrial protein and is the rate-limiting step in the generation of acetyl CoA from glycolysis. In IDDM, PDH activity is decreased through a mechanism that includes the stimulation of the de novo synthesis of a kinase activator protein (KAP) which phosphorylates PDH and inactivates the enzyme. This lesion does not occur in NIDDM rat hearts. Taurine is known to inhibit the phosphorylation of PDH in vitro, and in taurine-depleted rats PDH phosphorylation is known to increase. Thus, the increased levels of taurine in the diabetic heart may be inhibiting this phosphorylation which in turn may be stimulating the synthesis of KAP through a negative feedback process. The main argument for this theory would be the lack of change in both the taurine levels and the activity of PDH in the NIDDM rat model.

25. Adv Exp Med Biol. 2000;483:497-501. (Animal Study)

Taurine fluxes in insulin dependent diabetes mellitus and rehydration in streptozotocin treated rats.

Rose SJ, Bushi M, Nagra I, Davies WE.

Department of Paediatrics, Heartlands Hospital, Birmingham, England.

The effect of streptozotocin induced diabetes mellitus and rehydration on brain taurine and brain water content was studied in 4 groups of rats. Two groups of rats with diabetes mellitus were used. In one group, taurine and brain water content were determined following induction of diabetes for one week. In the second group, diabetes was induced for one week but before sacrifice, 15% of body weight of normal saline was introduced into the peritoneum, half at time 0, half 30 minutes later with sacrifice 60 minutes after the first infusion. In two groups of animals (controls), the brain taurine and water content were estimated in normal conditions and after hydration, in exactly the same way as diabetic rats. Brain taurine content was greater in diabetic rats than non-diabetic rats and there was no decrease in brain taurine content within the first hour following rehydration of the diabetic rats. Brain water content was greater in rehydrated diabetic rats than in non-rehydrated diabetic rats but there was no significant change in the brain water content after hydration of non diabetic rats. This suggested that the rapid change in water content of rehydrated diabetic rats was not accompanied by an equally rapid alteration in brain taurine content. This is consistent with the hypothesis that taurine flux could be a major factor in the aetiology of diabetic cerebral oedema. It also allows the development of possible therapeutic options which may increase outward taurine flux from brain cells. Taurine flux is increased by increasing extracellular sodium concentration or decreasing potassium concentration. Phospholemman channels may also influence taurine flux. These may have implications for the optimal method of clinical rehydration undertaken in diabetic ketoacidosis.

26. Am J Clin Nutr. 2000 Jan;71(1):54-8. (Animal Study)

Taurine improves insulin sensitivity in the Otsuka Long-Evans Tokushima Fatty rat, a model of spontaneous type 2 diabetes.

Nakaya Y, Minami A, Harada N, Sakamoto S, Niwa Y, Ohnaka M.

Department of Nutrition, Tokushima University, School of Medicine, Tokushima, Japan. nakaya@nutr.med.tokushima-u.ac.jp

BACKGROUND: Taurine, a potent antioxidant, has been reported to improve streptozotocin-induced diabetes mellitus, in which the development of diabetes results from an attack by oxygen free radicals on pancreatic beta cells. However, taurine also increases the excretion of cholesterol via conversion to bile acid and would be expected to improve insulin resistance. OBJECTIVE: The effects of taurine on insulin sensitivity were examined in a model rat of insulin resistance and type 2 diabetes-the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. DESIGN: Male OLETF rats were divided into 2 groups at the age of 16 wk: a taurine-supplemented group and an unsupplemented group. As a nondiabetic control, Long-Evans-Tokushima-Otsuka rats were used. An oral-glucose-tolerance test and hyperinsulinemic euglycemic clamp were performed at the ages of 23 and 25 wk. RESULTS: The OLETF rats had hyperglycemia and insulin resistance and they had a greater accumulation of abdominal fat than did control rats. Abdominal fat accumulation, hyperglycemia, and insulin resistance were significantly lower in the taurine-supplemented group than in the unsupplemented group. Serum and liver concentrations of triacylglycerol and cholesterol were significantly higher in the OLETF rats than in the control rats and were significantly lower in the taurine-supplemented group than in the unsupplemented group, presumably because of the increased secretion of cholesterol into bile acid. Taurine-supplemented rats also showed higher nitric oxide secretion, evidenced by increased urinary excretion of nitrite. CONCLUSION: Taurine effectively improves metabolism in OLETF rats by decreasing serum cholesterol and triacylglycerol, presumably via increased secretion of cholesterol into bile acid and decreased production of cholesterol because of increased nitric oxide production.

27. Adv Exp Med Biol. 1998;442:163-8. (Animal Study)

Effects of taurine supplementation on lipid peroxidation, blood glucose and blood lipid metabolism in streptozotocin-induced diabetic rats.

You JS, Chang KJ.

Department of Food Nutrition, Inha University, Inchon, Korea.

The purpose of this study was to determine the effect of taurine on several complications of diabetes, including oxidative stress, glucose intolerance and blood lipid profile. Sprague Dawley male rats were fed an experimental diet for 7 weeks, at which time they were maintained on drinking water with or without 1% taurine. The experimental period was 7 weeks and the rats were administered streptozotocin (STZ) to induce diabetes. Thiobarbituric acid reactive substances (TBARS) content was increased following the STZ injection, but was lowered by prior treatment with taurine. The primary diabetic symptoms, such as polydipsia and polyuria, were ameliorated in rats supplemented with taurine before the STZ injection. Plasma triglyceride (TG) levels of the diabetic group were decreased by taurine supplementation, although plasma total cholesterol (T-chol) and HDL cholesterol (HDL-chol) were not different among the groups. LDL cholesterol (LDL-chol) levels of the control group were significantly decreased by taurine supplementation, however, the time of taurine administration affected the response of the diabetic group; only diabetic rats treated with taurine after the administration of STZ showed a decrease in LDL cholesterol. Therefore, taurine inhibits lipid peroxidation and decreases blood TG and LDL-chol levels, however, the time and dose of taurine supplementation are variables that need to be considered in the treatment of diabetes.

28. Eur J Pharmacol. 1996 May 6;303(1-2):47-53. (Animal Study)

Restoration of endothelium-dependent relaxation in both hypercholesterolemia and diabetes by chronic taurine.

Kamata K, Sugiura M, Kojima S, Kasuya Y.

Department of Physiology and Morphology, Hoshi University, Tokyo, Japan.

We examined the effects of taurine on levels of low-density lipoprotein (LDL) cholesterol and glucose, and an endothelium-dependent relaxation in response to acetylcholine in cholesterol-fed or streptozotocin-induced diabetic mice. The acetylcholine-induced concentration-dependent relaxation was significantly attenuated in aortic rings from cholesterol-fed and streptozotocin-induced diabetic mice. The attenuated vasodilation in both cholesterol-fed and streptozotocin-induced diabetic mice was normalized by the chronic administration of taurine. The endothelium-independent relaxation of aortic rings induced by sodium nitroprusside was not significantly different between control, cholesterol-fed and streptozotocin-induced diabetic mice. The increased serum levels of LDL cholesterol in cholesterol-fed and diabetic mice were returned to normal by the chronic administration of taurine. The chronic administration of taurine had no effects on serum glucose levels. These results suggest that the impaired endothelium-dependent vasodilation seen in both cholesterol-fed and streptozotocin-diabetic mice can be normalized by the chronic administration of taurine and this effect may be, at least in part, due to lowering of serum LDL levels.

29. Am J Physiol. 1995 Sep;269(3 Pt 2):F429-38. (Animal Study)

Taurine ameliorates chronic streptozocin-induced diabetic nephropathy in rats.

Trachtman H, Futterweit S, Maesaka J, Ma C, Valderrama E, Fuchs A, Tarectecan AA, Rao PS, Sturman JA, Boles TH, et al.

Department of Pediatrics, Schneider Children's Hospital, Long Island Jewish Medical Center, Albert Einstein College of Medicine, New Hyde Park, New York 11040, USA.

We examined the effect of two endogenous antioxidant agents, taurine and vitamin E, on renal function in experimental diabetes. Male Sprague-Dawley rats, rendered diabetic with streptozocin (STZ), were assigned to one of the following groups: 1) untreated; 2) insulin treatment with 6 U Ultralente insulin/day in two doses; 3) taurine supplementation by 1% taurine in drinking water; and 4) vitamin E supplementation at 100 IU vitamin E/kg chow. Animals were kept for 52 wk. The survival rate was similar (70-90%) in all groups except vitamin E-treated animals, of which 84% died by 6 mo. At 52 wk, glomerular filtration rate was elevated in untreated and taurine-treated STZ rats compared with normal or insulin-treated diabetic rats. Taurine supplementation reduced total proteinuria and albuminuria by nearly 50%. This treatment also prevented glomerular hypertrophy, preserved immunohistochemical staining for type IV collagen in glomeruli, and diminished glomerulosclerosis and tubulointerstitial fibrosis in diabetic animals. The changes in renal function and structure in taurine-treated diabetic rats were associated with normalization of renal cortical malondialdehyde content, lowering of serum free Fe2+ concentration, and decreased formation of the advanced glycooxidation products, pentosidine, and fluorescence in skin collagen. Administration of the vitamin E-enriched diet exacerbated the nephropathy in STZ-diabetic rats. In addition, vitamin E supplementation increased serum free Fe2+ concentration, enhanced renal lipid peroxidation, and accelerated the accumulation of advanced glycosylation end products (AGEs) in skin collagen. We conclude that administration of taurine, but not vitamin E, to rats with STZ-diabetes ameliorates diabetic nephropathy. The beneficial effect of taurine is related to reduced renal oxidant injury with decreased lipid peroxidation and less accumulation of AGEs within the kidney.

30. Biochem Biophys Res Commun. 1993 Mar 15;191(2):759-65. (Animal Study)

Taurine prevents glucose-induced lipid peroxidation and increased collagen production in cultured rat mesangial cells.

Trachtman H, Futterweit S, Bienkowski RS.

Division of Nephrology, Schneider Children's Hospital, New Hyde Park, NY 11042.

Hyperglycemia is directly involved in the development of diabetic nephropathy. A high glucose concentration promotes membrane lipid peroxidation and stimulates collagen production in a variety of cultured cells. Taurine, a sulfur amino acid, is an endogenous antioxidant and antifibrotic agent. We tested whether taurine ameliorates the above effects of elevated ambient glucose on renal cells in vitro. Raising glucose concentration from 5.6 to 33.3 mM enhanced lipid peroxidation in rat mesangial cells, as assessed by malondialdehyde and conjugated diene content, and increased collagen production by 59%. Taurine prevented both glucose-induced effects in mesangial cells. In contrast, neither high glucose nor taurine, alone or in combination, affected lipid peroxidation or collagen production in MDCK or LLC-PK1 cells, derived from renal tubular epithelium. These results indicate that taurine may be a useful therapeutic agent to attenuate diabetic glomerulosclerosis.

31. Biochem Med Metab Biol. 1990 Feb;43(1):1-9. (Animal Study)

Supplemental taurine in diabetic rats: effects on plasma glucose and triglycerides.

Goodman HO, Shihabi ZK.

Department of Pediatrics, Bowman Gray School of Medicine, Winston-Salem, North Carolina 27103.

The present study has indicated that significant shifts in plasma, urinary, and tissue taurine and in non-taurine dialyzable amines occur in the STZ-induced diabetic rat, especially in the kidney. Taurine administration at relatively low dosage ameliorated only kidney taurine concentration. Anticipated alterations in plasma glucose and creatinine were observed but neither of these changes was affected by taurine administration. Similarly, urinary output of creatinine, glucose, and NAG increased significantly among diabetic rats, but none of these were detectably influenced by taurine. Increases in plasma triglycerides observed in STZ-induced diabetes appear to be attenuated by taurine administration, and although cholesterol concentrations were lower in taurine-treated rats, the differences were not statistically significant. These findings should encourage further studies of these effects in rats as a useful model for several complications of human diabetes including atherosclerosis, retinopathy, and nephropathy.

32. Probl Endokrinol (Mosk). 1987 Mar-Apr;33(2):63-6.

[Effect of taurine on the functional status of the insular apparatus and adrenal cortex of the rat with experimental diabetes]

[Article in Russian]

Mizina TIu, Dokshina GA.

The effect of taurine on the regulation of function of the insular apparatus and adrenal cortex of rats with experimental alloxan diabetes was studied. The assessment of the state of the endocrine glands was based on the determination of the content of immunoreactive insulin, total, free and protein-bound 11-oxycorticosteroids (11-OCS) in the blood of rats and a study of the secretory ability of the adrenals and pancreatic fragments in vitro. A single administration of taurine (300 mg/kg per os) to the rats with experimental alloxan diabetes was accompanied by the reduction of the content of immunoreactive insulin, total and free 11-OCS in the blood, a secretory ability of the adrenal cortex and insulin excretory function of the pancreas. The ability of the pancreatic islet tissue to produce insulin in vitro in response to the natural stimulator glucose was disturbed in the rats with experimental diabetes. Taurine (12 mumol/ml) added to the incubation medium containing isolated adrenals and fragments of the pancreas from the diabetic animals, caused a decrease in a high secretory ability of the cortical substance of the adrenal glands and a partial reduction of the insulin secretory ability of the pancreatic tissue.

Hypoxia

33. Psychopharmacology (Berl). 1989;98(3):316-20. (Animal Study)

Effect of ICV taurine on the impairment of learning, convulsions and death caused by hypoxia.

Malcangio M, Bartolini A, Ghelardini C, Bennardini F, Malmberg-Aiello P, Franconi F, Giotti A.

Department of Preclinical and Clinical Pharmacology, University of Florence, Firenze, Italy.

The effect of the intracerebroventricular (ICV) administration of taurine on amnesia, convulsions and death caused by hypoxia was investigated in mice. Taurine in doses of 80-100 micrograms/mouse impaired acquisition of a single trial in passive avoidance performance, but protected mice from the learning impairment induced by hypoxia. Neither beta-alanine nor saccharose were able to mimic the effects of taurine. Taurine had no effect on amnesia induced by scopolamine injected intraperitoneally. Taurine protected against the onset of convulsions induced by hypoxia, while convulsions induced by pentylenetetrazole (PTZ) and hyperbaric oxygen were unaffected. The survival time of mice exposed to hypoxia was significantly increased by taurine treatment. These data suggest that taurine may play a role as an antihypoxic agent.

34. Eur J Pharmacol. 1986 Jan 21;120(2):235-9.

Protective effect of taurine against decline of cardiac slow action potentials during hypoxia.

Sawamura A, Sperelakis N, Azuma J.

The effect of taurine on cardiac slow action potentials (APs) during hypoxic superfusion was studied in isolated guinea-pig papillary muscles. Ca2+-dependent slow APs were induced by isoproterenol (10(-6) M) in preparations which were voltage-inactivated by high (25 mM) K+. Although taurine had no effect on the slow AP parameters during normoxia, taurine (10 mM) superfusion significantly protected against the decline of slow APs produced by hypoxia. Taurine also restored slow APs that had been previously abolished by hypoxia. Therefore, taurine exposure may protect the Ca2+ slow channels which are inhibited or blocked by hypoxic conditions. Biochem Pharmacol. 1985 Aug 1;34(15):2611-5. (Animal Study)

35. The protective effects of taurine on hypoxia (performed in the absence of glucose) and on reoxygenation (in the presence of glucose) in guinea-pig heart.

Franconi F, Stendardi I, Failli P, Matucci R, Baccaro C, Montorsi L, Bandinelli R, Giotti A.

In isolated guinea-pig heart submitted to hypoxia in the absence of substrate and subsequent reoxygenation 1-20 mM taurine decreases LDH release and ventricular arrhythmias, and the recovery of normal electrical and mechanical activity is increased. The taurine effect is dose-dependent, and is not mimicked by beta-alanine. Moreover, taurine reduces the increase in calcium gain of reoxygenated heart.

Antiatherogenic

36. Indian J Exp Biol. 2002 Oct;40(10):1169-72.

Antiatherogenic effect of taurine in high fat diet fed rats.

Sethupathy S, Elanchezhiyan C, Vasudevan K, Rajagopal G.

Division of Biochemistry, Rajah Muthiah Medical College, Annamalai University, Annamalai Nagar 608 002, India. drsethupathy@rediffmail.com

The role of taurine on atherogenesis induced by high fat diet in rats, a species which depends entirely on taurine for conjugation of bile acids has been investigated. Wistar male rats were fed on (p.o.) taurine in addition to high fat diet (11% coconut oil w/w) for 6 months. High fat diet caused significant increase of serum total cholesterol (2 fold), serum triglycerides (92.6%), LDL cholesterol (92.3%) and body weight gain (2.8 fold). Taurine administration significantly reduced serum cholesterol (37%), triglycerides (94.5%), LDL cholesterol (34%), body weight (46%). It also significantly reduced aortic cholesterol and thiobarbituric acid reactive substances and there was a significant increase of reduced glutathione. Taurine significantly increased fecal bile acids which may have resulted in significant decrease of serum cholesterol. Aortic lesion index was significantly decreased in the taurine administered group suggesting the antiatherogenic effect of taurine. It is concluded that taurine attenuated the atherogenesis possibly by its hypocholesterolemic and antioxidant property.

Membrane Stabilizer

37. J Nutr Sci Vitaminol (Tokyo). 1995 Dec;41(6):627-34.

Effects of taurine on depletion of erythrocyte membrane Na-K ATPase activity due to ozone exposure or cholesterol enrichment.

Qi B, Yamagami T, Naruse Y, Sokejima S, Kagamimori S.

Department of Community Health and Preventive Medicine, Toyama Medical and Pharmaceutical University, Japan.

The objective of this study was to investigate the interrelationship between taurine and erythrocyte-membrane Na-K ATPase activity. A comparison was conducted to test whether taurine or uric acid (a water-soluble scavenger of free radicals) prevents or recovers the depletion in membrane ouabain-sensitive Na-K ATPase activity resulting from ozone exposure or cholesterol enrichment of the erythrocyte membrane. A depletion of 44% and 27% in ouabain-sensitive Na-K ATPase activity was respectively caused by ozone exposure and cholesterol enrichment. Taurine as well as uric acid partially prevented the activity loss from ozone exposure. In addition, taurine at high concentrations (from 1.5 to 4.5 mM) restored the depletion of erythrocyte-membrane Na-K ATPase activity due to ozone exposure and prevented the depletion of the enzyme activity due to cholesterol enrichment. In contrast, although the same high concentrations were used, uric acid failed to show either of the above effects. These results suggest that taurine acts (1.5-4.5 mM) polyvalently as not only an antioxidizing agent but also as a membrane stabilizer to maintain the functions of membrane Na-K ATPase, a membrane-bound protein.

Seizures

38. Adv Exp Med Biol. 2003;526:515-25. (Animal Study)

Prevention of epileptic seizures by taurine.

El Idrissi A, Messing J, Scalia J, Trenkner E.

New York State Institute for Basic Research in Developmental Disabilities and The Center for Developmental Neuroscience, The City University of New York, Staten Island, NY 10314, USA.

Parenteral injection of kainic acid (KA), a glutamate receptor agonist, causes severe and stereotyped behavioral convulsions in mice and is used as a rodent model for human temporal lobe epilepsy. The goal of this study is to examine the potential anti-convulsive effects of the neuro-active amino acid taurine, in the mouse model of KA-induced limbic seizures. We found that taurine (43 mg/Kg, s.c.) had a significant antiepileptic effect when injected 10 min prior to KA. Acute injection of taurine increased the onset latency and reduced the occurrence of tonic seizures. Taurine also reduced the duration of tonic-clonic convulsions and mortality rate following KA-induced seizures. Furthermore, taurine significantly reduced neuronal cell death in the CA3 region of the hippocampus, the most susceptible region to KA in the limbic system. On the other hand, supplementation of taurine in drinking water (0.05%) for 4 continuous weeks failed to decrease the number or latency of partial or tonic-clonic seizures. To the contrary, we found that taurine-fed mice showed increased susceptibility to KA-induced seizures, as demonstrated by a decreased latency for clonic seizures, an increased incidence and duration of tonic-clonic seizures, increased neuronal death in the CA3 region of the hippocampus and a higher post-seizure mortality of the animals. We suggest that the reduced susceptibility to KA-induced seizures in taurine-injected mice is due to an increase in GABA receptor function in the brain which increases the inhibitory drive within the limbic system. This is supported by our in vitro data obtained in primary neuronal cultures showing that taurine acts as a low affinity agonist for GABA(A) receptors, protects neurons against kainate excitotoxic insults and modulates calcium homeostasis. Therefore, taurine is potentially capable of treating seizure-associated brain damage.

39. Amino Acids. 1999;16(2):133-47. (Animal Study)

Kainic acid (KA)-induced seizures in Sprague-Dawley rats and the effect of dietary taurine (TAU) supplementation or deficiency.

Eppler B, Patterson TA, Zhou W, Millard WJ, Dawson R Jr.

Department of Pharmacodynamics, University of Florida, Gainesville, USA.

Male Sprague-Dawley rats received TAU supplementation (1.5% in drinking water) or TAU deficient diets for 4 weeks to test for a possible neuroprotective role of TAU in KA-induced (10 mg/kg s.c.) seizures. TAU supplementation significantly increased serum and hippocampal TAU levels, but not TAU content in temporal cortex or striatum. TAU deficient diets did not attenuate serum or tissue TAU levels. Dietary TAU supplementation failed to decrease the number or latency of partial or clonic-tonic seizures or wet dog shakes, whereas a TAU deficient diet decreased the number of clonictonic and partial seizures. This study does not support previous observations of an anticonvulsant effect of TAU against KA-induced seizures. KA-treatment decreased alpha 2-adrenergic receptor binding sites and TAU content in the temporal cortex across all dietary treatment groups, supporting previous evidence of severe KA-induced damage and neuronal loss in this brain region.

40. Yakubutsu Seishin Kodo. 1991 Aug;11(4):257-60. (Animal Study)

[Drug-induced seizures in taurine-deficient mice]

[Article in Japanese]

Shimada C, Tanaka S, Sano M, Araki H.

Research and Development Center, Fuso Pharmaceutical Industries, Ltd., Osaka, Japan.

Appearances of pentetrazole-, picrotoxin- and strychnine-induced convulsive seizures in taurine-deficient mice produced by treatment with guanidinoethyl sulfonate (GES), a taurine transport antagonist, were investigated. Mice were fed a taurine-free diet and water containing 1% GES from 2 weeks of pregnancy to weaning. The same feeding condition was applied to male offsprings from 3 weeks of age. At 5 weeks of age, convulsants were administered to some mice and the others were sacrificed for determination of brain amino acids concentrations. The incidences of both seizure and death for strychnine and death for picrotoxin were enhanced by treatment with GES, whereas the latency of pentetrazole-induced tonic extensor was prolonged. Significant decrease of brain taurine, asparaginic acid and GABA concentrations were observed in mice treated with GES. These results suggest that convulsive seizures caused by disinhibition of taurine and GABA system are enhanced by deficiency of brain taurine level.

41. Neuropharmacology. 1987 Dec;26(12):1721-5.

Higher susceptibility of taurine-deficient rats to seizures induced by 4-aminopyridine.

Pasantes-Morales H, Arzate ME, Quesada O, Huxtable RJ.

Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, D.F.

The susceptibility of rats made deficient of taurine by treatment with guanidinoethane sulfonate (GES), to seizures induced by 4-aminopyridine was examined. Guanidinoethane sulfonate, at a concentration of 1% was administered to pregnant rats, in the drinking water 2-3 days prior to delivery and the treatment was continued during nursing. Pups were weaned to the same treatment until 6 weeks of age. This treatment decreased levels of taurine in the cerebral cortex by 70%. 4-Aminopyridine was injected intraperitoneally at doses ranging from 4-7 mg/kg. Taurine-deficient rats showed a greater susceptibility to seizures, as demonstrated by a lowered latency for clonic seizures, an increased incidence of tonic seizures and a higher postseizure mortality. These results suggest an involvement of endogenous taurine in nervous excitability.

42. Med Hypotheses. 1985 Dec;18(4):411-5.

Could supplementary dietary tryptophan and taurine prevent epileptic seizures?

Maurizi CP.

Roles for melatonin, taurine, and the pineal gland in epilepsy are examined. Cerebrospinal fluid melatonin and taurine may be natural anticonvulsants. The flow of cerebrospinal fluid may bathe the medial and lateral geniculate ganglia and the superior and inferior colliculli with these anticonvulsant substances. Supplemental dietary taurine and tryptophan could be of value in the treatment and prevention of seizures.

43. J Neurosci Res. 1981;6(4):465-74.

Effect of taurine on seizures induced by 4-aminopyridine.

Pasantes-Morales H, Arzate ME.

The effect of intraperitoneally injected taurine against the convulsive activity induced by 4-aminopyridine (4-AP) was studied in 12- to 15-day-old mice. At a dose of 2.6 mg/kg, taurine increased the latency of clonic seizures from 7 to 20 minutes, reduced the incidence of tonic seizures from 92% to 30% and the postconvulsive mortality from 80% to 31%. The injection of EDTA prior to the administration of taurine prevented the protective effects of the amino acid. GABA and glycine at the same doses did not protect against 4-AP-induced seizures. 4-AP caused a small increase (19%) in 45Ca accumulation by mice brain synaptosomes incubated in a Krebs-HEPES medium containing low CaCl2 (0.1 mM) and also slightly potentiated the veratrine and potassium-induced increase in calcium accumulation. 4-AP at concentrations of 1-2 mM caused a marked increase (100%-500%) of 45 Ca accumulation by synaptosomes incubated in a Krebs-bicarbonate medium containing 2.5 mM CaCl2. This increase was completely antagonized by taurine but not by GABA of glycine. The present observations suggest that the anticonvulsant effect of taurine might be mediated by 4-AP-calcium-taurine interactions.

44. J Neural Transm. 1980;48(4):311-6. (Animal Study)

Taurine selectivity antagonizes L-kynurenine-produced seizures in mice.

Lapin IP.

Taurine in doses of 100 and 200 mg/kg (intraperitoneally) and 2.5 micrograms (into brain ventricles) antagonized clonic seizures produced by L-kynurenine sulfate injected into brain ventricles of SHR adult male albino mice. Seizures produced by another metabolite of tryptophan in the kynurenine pathway, quinolinic acid, were intensified. The convulsant effects of strychnine, pentylenetetrazol and thiosemicarbazide was not modified.

45. Can J Physiol Pharmacol. 1978 Jun;56(3):497-500. (Animal Study)

The effect of taurine on kindled seizures in the rat.

Burnham WM, Albright P, Racine RJ.

Recently, it has been reported that taurine, an amino acid with anticonvulsant properties, does not suppress experimental seizures generated by the "kindling" technique. This finding seems somewhat paradoxical since taurine antagonizes other sorts of experimental convulsion and since kindled seizures are easily suppressed by other anticonvulsant drugs. Further tests were therefore conducted during which taurine's anticonvulsant effects were assessed: (1) when kindling stimulation was dropped to near-threshold levels; (2) when cortical as well as limbic kindled foci were stimulated; (3) when developing as well as fully kindled seizures were involved; and (4) when taurine was introduced directly into the ventricles of the brain. Even in these tests which were specifically designed to favour the appearance of anticonvulsant effects, no taurine antagonism of kindled seizures was found.

46. Epilepsia. 1975 Jun;16(2):229-34.

Effects of taurine on kindled amygdaloid seizures in rats, cats, and photosensitive baboons.

Wada JA, Osawa T, Wake A, Corcoran ME.

Acute administration of taurine produced a transient loss of susceptibility to photically induced seizures in photosensitive baboons, but failed to affect kindled amygdaloid convulsions in baboons, rats, and cats. In addition, it was totally ineffective in changing the course of spontaneous status epilepticus in kindled cats. These results suggest that a taurine-deficiency model of epilepsy applies only to certain types of seizure-generating conditions, apparently excluding kindled amygdaloid convulsions.

Memory

47. Neural Plast. 2000;7(4):245-59. (Animal Study)

Improvement of impaired memory in mice by taurine.

Vohra BP, Hui X.

Department of Biotechnology, School of Life Sciences, Sun-Yat-Sen University, Guangzhou, China-510 275. Vohra001@tc.umn.edu

Taurine was extracted from Pegasus laternarius Cuvier to study its effects on learning and memory in mice. Mice were treated with different doses of taurine (10 mg/kg, 20 mg/kg, 40 mg/kg). The mice were treated with various chemical agents (pentobarbital, cycloheximide, sodium nitrite, alcohol) to disrupt the normal memory process. We measured the effect of taurine on step-down latency (SDL) and escape latency (EL) in a passive avoidance task after 10 or 30 days. Treatment with taurine alone did not change either SDL or EL. Taurine protected mice from the memory disruption induced by alcohol, pentobarbital, sodium nitrite, and cycloheximide but had no obvious effect on motor coordination, exploratory activity, or locomotor activity as measured using the rota-rod test and the hole board test. We conclude that taurine can be effective in attenuating the amnesia produced by alcohol, pentobarbital, cycloheximide, and sodium nitrite without compromising the behavioral aspects of the animals tested.

48. Environ Res. 2000 Jan;82(1):7-17.

Effects of taurine on ozone-induced memory deficits and lipid peroxidation levels in brains of young, mature, and old rats.

Rivas-Arancibia S, Dorado-Martinez C, Borgonio-Perez G, Hiriart-Urdanivia M, Verdugo-Diaz L, Duran-Vazquez A, Colin-Baranque L, Avila-Costa MR.

Departamento de Fisiologia, Facultad de Medicina, Universidad Nacional Autonoma de Mexico, Mexico.

To determine the antioxidant effects of taurine on changes in memory and lipid peroxidation levels in brain caused by exposure to ozone, we carried out two experiments. In the first experiment, 150 rats were separated into three experimental blocks (young, mature, and old) with five groups each and received one of the following treatments: control, taurine, ozone, taurine before ozone, and taurine after ozone. Ozone exposure was 0.7-0.8 ppm for 4 h and taurine was administered ip at 43 mg/kg, after or before ozone exposure. Subsequently, rats were tested in passive avoidance conditioning. In the second experiment, samples from frontal cortex, hippocampus, striatum, and cerebellum were obtained from 60 rats (young and old), using the same treatments with 1 ppm ozone. Results show both an impairment in short-term and long-term memory with ozone and an improvement with taurine after ozone exposure, depending on age. In contrast to young rats, old rats showed peroxidation in all control groups and an improvement in memory with taurine. When taurine was applied before ozone, we found high peroxidation levels in the frontal cortex of old rats and the hippocampus of young rats; in the striatum, peroxidation caused by ozone was blocked when taurine was applied either before or after ozone exposure.

Cystic Fibrosis

49. Arch Dis Child. 1992 Sep;67(9):1082-5.

Effect of taurine supplementation on fat and energy absorption in cystic fibrosis.

De Curtis M, Santamaria F, Ercolini P, Vittoria L, De Ritis G, Garofalo V, Ciccimarra F.

Department of Paediatrics, 2nd School of Medicine, University of Naples, Italy.

In 10 children with cystic fibrosis and persisting steatorrhoea, supplementation with taurine (30-40 mg/kg/day) was given for two months as an adjunct to the usual pancreatic enzyme treatment. A three day fat and energy balance was performed in patients with cystic fibrosis, before and after the supplementation, and in seven healthy controls who did not receive taurine. Faecal fat was measured by a gravimetric method and stool energy was determined using a bomb calorimeter. Patients with cystic fibrosis, before and after taurine, and healthy controls received the same fat and energy intake (calculated by a dietitian). In patients with cystic fibrosis taurine did not produce any improvement of steatorrhoea (mean (SD) faecal fat 8.7 (3.3) v 11.2 (7.0) g/day, respectively before and after the supplementation), of faecal energy loss (0.978 (0.468) v 1.133 (0.539) MJ/day), of faecal fat expressed as percent of fat intake (13.4 (5.6) v 15.1 (9.8)%), and of faecal energy expressed as percent of energy intake (9.9 (3.6) v 11.2 (5.7)%). Healthy controls had significant lower fat (3.5 (2.3) g/day) and energy 0.576 (0.355) MJ/day faecal losses. In conclusion, taurine failed to decrease significantly fat and energy losses. Our study does not support the use of taurine supplementation in the nutritional management of cystic fibrosis.

50. Am J Dis Child. 1991 Dec;145(12):1401-4.

Taurine decreases fecal fatty acid and sterol excretion in cystic fibrosis. A randomized double-blind trial.

Smith LJ, Lacaille F, Lepage G, Ronco N, Lamarre A, Roy CC.

Department of Pediatrics, Hopital Ste-Justine, Montreal, Quebec, Canada.

Patients with cystic fibrosis may still have a significant degree of steatorrhea despite adequate pancreatic enzyme supplementation. Taurine is a conditionally essential amino acid that possibly improves the micellar phase of fat digestion. Thirteen children with cystic fibrosis and a significant degree of steatorrhea (> 13 g/d) were enrolled in a randomized double-blind crossover study of taurine (30 mg/kg per day) in contrast to placebo for two successive 4-month periods. No difference was noted in height and weight velocity, lung function, vitamin A level, and essential fatty acid status. Twelve of the 13 patients showed a decrease in fecal fatty acid excretion (26.5 +/- 2.6 g/24 h vs 15.4 +/- 2.5 g/24 h), affecting mainly saturates and monounsaturates, and a decrease in total sterol excretion (1492.6 +/- 303 mg/24 h vs 1211.7 +/- 213.8 mg/24 h) while ingesting taurine. Taurine may be a useful adjunct in patients with cystic fibrosis and severe steatorrhea.

51. Klin Padiatr. 1991 Jan-Feb;203(1):28-32.

[Taurine supplementation in cystic fibrosis (CF): effect on vitamin E absorption kinetics]

[Article in German]

Skopnik H, Kusenbach G, Bergt U, Friedrichs F, Stuhlsatz H, Dohmen H, Heimann G.

Kinderklinik, RWTH Aachen.

Oral vitamin E (Vit.E) bioavailability is reduced in CF patients especially in case of malnourishment. Both exocrine pancreatic insufficiency and an altered bile acid composition showing an elevated glycine taurine ratio of conjugated bile acids which is due to excessive loss of bile acids in the stools may contribute to this observation. Because taurine supplementation reduces the glycine/taurine ratio of bile acids in duodenal juice of CF-patients it was the objective of this study to evaluate the effect of taurine supplementation on Vit.E absorption kinetics. Oral Vit.E tolerance tests (50 mg/kg) were performed before and after 3 months of taurine supplementation (30 mg/kg/day) in 11 CF patients (ages 7 to 22 years) under fasting conditions. Bodyweight and or weight for height of all patients were below the 25th percentile. Doses of all medications except antibiotics were kept unchanged during the study. Any additional Vit.E supplementation was stopped 14 days prior to each test. Serum Vit.E levels were measured over a 24 hour period. Determination of serum Vit.E concentrations was performed with a HPLC fluorescence technique. The glycine/taurine ratio in serum served as compliance parameter and dropped in all but one patients. Baseline Vit.E concentrations and serum Vit.E/total lipids ratios in serum considered as parameters of the Vit.E status increased significantly. Both the maximal Vit.E concentrations in serum and the areas under the oral absorption curves showed a significant increase with taurine supplementation. This study shows that the Vit.E status of malnourished CF patients can be improved with taurine supplementation due to improved Vit.E absorption kinetics.(ABSTRACT TRUNCATED AT 250 WORDS)

52. Acta Univ Carol [Med] (Praha). 1990;36(1-4):152-6.

Effect of taurine supplements on growth, fat absorption and bile acid on cystic fibrosis.

Carrasco S, Codoceo R, Prieto G, Lama R, Polanco I.

Department of Pediatrics, Children's Hospital La Paz, Autonoma University, Madrid, Spain.

We have evaluated the effect of taurine supplementation nutritional status, steatorrhea and bile acid in twenty two Cystic Fibrosis patients. Weight increased in fifty per cent and height in forty eight per cent of them. Steatorrhea improved significantly in six patients of group II. Glycine/taurine ratio was reduced. Bile acid malabsorption improved only in the patients with high degree of steatorrhea. Serum bile acid was observed significantly elevated in both groups. This results suggest that taurine supplementation can be useful adjunct from of therapy in Cystic Fibrosis patients with fat malabsorption.

53. Biochem Cell Biol. 1988 Jul;66(7):702-6.

Taurine uptake by normal and cystic fibrosis fibroblasts.

Thompson GN.

Department of Chemical Pathology, Adelaide Children's Hospital, North Adelaide, Australia.

Taurine deficiency recently has been proposed to be clinically significant in cystic fibrosis (CF). Uptake of [14C]taurine by four cystic fibrosis (CF) and three control fibroblast lines was examined to determine whether a generalized defect in taurine transport could contribute to the deficiency. The time course of uptake was linear up to 20 h and was similar in both CF and control fibroblasts. Taurine was avidly retained after uptake, and the effect of metabolic (chlorpromazine) and competitive (hypotaurine, L-leucine) inhibitors was similar in both CF and control cells. In contrast, while taurine uptake in a calcium-free medium was impaired in both CF and control fibroblasts, the impairment was significantly less in CF cells. The findings suggest that a generalized abnormality in taurine transport is unlikely to be responsible for the taurine deficiency in CF.

54. J Pediatr Gastroenterol Nutr. 1988 Mar-Apr;7(2):214-9.

Excessive fecal taurine loss predisposes to taurine deficiency in cystic fibrosis.

Thompson GN.

Department of Chemical Pathology, Adelaide Children's Hospital, South Australia.

Elevation of the ratio of glycine: taurine-conjugated bile acids (G/T ratio) is thought to contribute to fat malabsorption in cystic fibrosis (CF). The cause, extent, and reversibility of taurine deficiency in CF were assessed using balance studies in 6 subjects (ages 8-14 years) who were supplemented with taurine (0.24-2.4 mmol/kg/24 h) for 1 week. Taurine reduced the G/T ratio both in serum and duodenal juice in all children. The mean fecal taurine loss in CF subjects [10.8 mumol/kg/24 h +/- 9.9 (SD), range 0.9-27.9] was much greater than that in controls (less than 0.1 mumol/kg/24 h, n = 4) and approximated the dietary taurine intake (mean 14.6 +/- 4.4 mumol/kg/24 h, n = 12). Absorption of an oral taurine load appeared to be normal in CF. Excessive fecal taurine loss appears to predispose CF children to bile acid taurine deficiency, a deficiency that can be corrected by oral taurine supplements.

55. Scand J Gastroenterol Suppl. 1988;143:151-6.

Effect of taurine supplementation on fat and bile acid absorption in patients with cystic fibrosis.

Colombo C, Arlati S, Curcio L, Maiavacca R, Garatti M, Ronchi M, Corbetta C, Giunta A.

Dept. of Pediatrics, University of Milan, Italy.

Eleven children with cystic fibrosis (CF) and pancreatic insufficiency were given supplementation with taurine (30-40 mg/kg/day) for 2 months, while taking their usual dosage of enzymatic therapy. One patient dropped out of the study because she developed severe constipation. In the other 10 patients, urinary taurine excretion (88 +/- 30.1 mg/m2s.a./24 h) was similar to that of controls (86.2 +/- 6 mg/m2s.a./24 h) before taurine and increased markedly after supplementation (618.2 +/- 79.97 mg/m2s.a./24 h), indicating efficient intestinal absorption. Their coefficient of fat absorption was 81.2 +/- 2.3% and increased significantly after taurine (91.3 +/- 1.13%; p less than 0.01); the area under the curve of plasma triglyceride postprandial levels (1 +/- 0.1 mg X min/ml) also increased significantly after taurine (1.4 +/- 0.3 mg X min/ml; p less than 0.05), showing values very similar to those of controls. Conversely, no change was observed in the serum postprandial levels of glycocholic acid: the maximum postprandial peak before (1.2 +/- 0.3 mumol/l) and after taurine (1 +/- 0.1 mumol/l) remained significantly lower than in controls (2.4 +/- 0.3 mumol/l); p less than 0.01 and p less than 0.001, respectively. Mean total fecal bile acid (BA) excretion was 10.24 +/- 2.15 mg/kg/day before taurine and 12.8 +/- 4.27 mg/kg/day after taurine (normal pediatric values, 2.91 +/- 1.1 mg/kg/day); however, in the individual patients we found a variable trend, four of them showing a net increase in fecal BA excretion.(ABSTRACT TRUNCATED AT 250 WORDS)

56. Am J Clin Nutr. 1987 Oct;46(4):606-13.

Protein metabolism in cystic fibrosis: responses to malnutrition and taurine supplementation.

Thompson GN, Tomas FM.

Department of Chemical Pathology, Adelaide Children's Hospital, South Australia.

Increased protein breakdown has been cited as an important cause of nutrient loss in cystic fibrosis (CF). Taurine deficiency, which is common in CF, may contribute to the increased breakdown. The occurrence of and the benefit of taurine supplementation to abnormal protein metabolism in apparently optimally treated CF were assessed using a 12-mo double-blind crossover technique in 14 well-nourished and seven mildly-moderately malnourished infection-free preadolescent CF children. Muscle protein breakdown (urinary 3-methylhistidine technique) was significantly decreased in well-nourished (1.35% degraded/24 h +/- 0.15, p less than 0.05) and malnourished (1.24 +/- 0.11, p less than 0.001) CF children compared with controls (1.50 +/- 0.17, n = 13). Whole-body protein flux, synthesis, and catabolism ([15N]-glycine technique) were similar in all groups. Net protein gain was greater in CF children, particularly those who were well-nourished (0.55 g/(kg X 10 h) +/- 0.35, p less than 0.01) compared with controls (0.16 +/- 0.26). Taurine supplementation did not significantly affect any of the indices. In the absence of infection, protein metabolism in CF children responds appropriately to malnutrition.

57. Pediatrics. 1987 Oct;80(4):517-23.

Taurine improves the absorption of a fat meal in patients with cystic fibrosis.

Belli DC, Levy E, Darling P, Leroy C, Lepage G, Giguere R, Roy CC.

Department of Pediatrics, Hopital Ste-Justine, Montreal, Quebec, Canada.

The effect of taurine supplementation on the absorption of a fat meal was evaluated in patients with cystic fibrosis. In a cross-over design study, five patients with cystic fibrosis (12.1 +/- 2.6 years of age) and three control subjects received either placebo or taurine (30 mg/kg/d) for two 1-week periods, a month apart, followed by a fat meal test. Blood samples were drawn 0, 1, 2, 3, 5, 8 hours after the meal. Four patients with cystic fibrosis and severe steatorrhea despite appropriate enzyme therapy showed a significant (P less than .05) improvement in the absorption of triglycerides, total fatty acids, and linoleic acid while receiving taurine supplements. Three control subjects and one child with cystic fibrosis and mild steatorrhea receiving enzyme therapy did not experience such an effect. The difference in triglyceride absorption, when calculated as the area under the curve, receiving and not receiving taurine was significantly (P less than .05) correlated with the degree of steatorrhea. Furthermore, in contrast to control subjects, the fatty acid composition of chylomicrons in these four study patients showed important discrepancies with that of the fat meal and was corrected, in part, by taurine supplementation. These results suggest that taurine supplementation could be a useful adjunct in the management of patients with cystic fibrosis with ongoing fat malabsorption and essential fatty acid deficiency.

58. Pediatr Res. 1985 Jun;19(6):578-82.

Effect of taurine supplements on fat absorption in cystic fibrosis.

Darling PB, Lepage G, Leroy C, Masson P, Roy CC.

Patients with cystic fibrosis have an increased proportion of glycine conjugated bile acids with diminished tauroconjugates which could contribute to fat malabsorption. Twenty-two CF children with documented steatorrhea were supplemented with taurine capsules (30 mg/kg/day) and placebo during separate 6-month treatment periods. Alteration of the glycine/taurine conjugation pattern was verified in two patients who showed a predominance of tauroconjugates as a result of taurine supplementation. On taurine, steatorrhea was reduced (p less than 0.05) by 17.6 +/- 9.7% in 19 patients who completed the study as was the excretion of long-chain saturated fatty acids. There was no change in linoleic acid (C 18:2) excretion. In the 10 patients with a more severe degree of steatorrhea the decrease in fat loss approached 20% and a close relationship was found (r = 0.84, p less than 0.01) between the extent of the fatty acid loss on placebo and the decrease of this loss on taurine. A linear relationship was found between the percentage decrease of individual fatty acids and their log solubility in water. No change was found in the daily excretion of bile acids, neutral sterols, and nitrogen. Fasting plasma fatty acids, cholesterol, and triglycerides were also unchanged. Monitoring of growth over the two 6-month periods revealed a marginal (p less than 0.1) increase of weight velocity expressed as a percentage expected for age (83.4 +/- 11.3----117.1 +/- 16.5). The increase in height velocity in response to taurine showed a more modest trend (95.3 +/- 7.8----110.7 +/- 10.6).(ABSTRACT TRUNCATED AT 250 WORDS)

Eye Lens

59. Invest Ophthalmol Vis Sci. 2002 Feb;43(2):425-33. (Animal Study)

Osmoregulatory alterations in taurine uptake by cultured human and bovine lens epithelial cells.

Cammarata PR, Schafer G, Chen SW, Guo Z, Reeves RE.

Department of Pathology and Anatomy, Division of Cell Biology and Genetics, University of North Texas Health Science Center at Fort Worth and the North Texas Eye Research Institute, Fort Worth, Texas 76107, USA. pcammara@hsc.unt.edu

PURPOSE: Comparative assessment of cultured human lens epithelial cells (HLECs) and bovine lens epithelial cells (BLECs) established the nature of the relationship between taurine-concentrating capability and intracellular polyol accumulation or extracellular hypertonicity. METHODS: The kinetic characteristics of active taurine accumulation based on the measurement of in vitro [3H]-taurine uptake were resolved by side-to-side review of cultured HLECs and BLECs pre-exposed to either galactose-supplemented medium or extracellular hypertonicity. Competitive RT-PCR was used to appraise variation in taurine transporter (TauT) mRNA abundance from cells maintained in hyperosmotic medium over a 72-hour exposure period. RESULTS: The capacity to accumulate [3H]-taurine was significantly lowered after prolonged (20-hour) incubation of cultured BLECs in 40 mM galactose in contrast to HLECs, the latter cells' velocity curve being indistinguishable from control cells in physiological medium. Inhibition of the intracellular taurine transport site appeared to be noncompetitive, in that there was a marked reduction in the V(max) without significant alteration in the K(m) to a high-affinity transport site. Galactitol content in BLECs exceeded five times that found in HLECs. The coadministration of the aldose reductase inhibitor, sorbinil, with 40 mM galactose completely prevented the inhibitory effect of galactose on [3H]-taurine uptake. Acute exposure (3 hours) of HLECs and BLECs to a range of 10 to 40 mM galactitol or 10 to 40 mM galactose plus sorbinil-supplemented medium suggested by Dixon plot that neither galactitol nor galactose interacted with the extracellular taurine transport site. In contrast, [3H]-taurine accumulation was markedly elevated in both HLECs and BLECs after prolonged exposure to galactose-free medium made hyperosmotic by supplementation with sodium chloride. The enhanced taurine uptake capacity involved increase in peak velocity (V(max)) without significant change in Michaelis-Menten constant (K(m)). Cultured HLECs and BLECs responded to hypertonicity with an inducible but transitory upregulation of TauT mRNA. CONCLUSIONS: These results demonstrate that lens epithelial cells express a high-affinity TauT protein capable of active uptake, but predisposed to inhibition by intracellular galactitol when the sugar alcohol is present in sufficiently high concentration to interfere with cell metabolism. Furthermore, lens epithelial cells respond to hypertonic stress by raising taurine transport activity. The increase in taurine uptake is due to an increase in the number of high-affinity TauTs expressed as a result of an increase in the manifestation of taurine mRNA stemming from exposure to hypertonic medium.

60. Zhonghua Yan Ke Za Zhi. 2000 Jul;36(4):272-4, 17. (Animal Study)

[An experimental research of taurine on H2O2-induced bovine lens epithelial cell apoptosis]

[Article in Chinese]

Chen F, Chen C.

Beijing Institute of Ophthalmology, Beijing 100005, China.

OBJECTIVE: To study the inhibitory role of taurine on H(2)O(2)-induced bovine lens epithelial cell apoptosis. METHODS: By terminal deoxyribonucleotide transferase-mediated dUTP nick end labeling (TUNEL) detection and bovine lens organ culture, we examined the affect of taurine on the number of H(2)O(2)-induced bovine lens epithelial cells with apoptosis, the related comparisons and statistic analyses were carried out. RESULTS: (1) Lens epithelial cell apoptosis began before lens opaqueness (lens became opaque after 6 hours of incubation, while the lens epithelial cell apoptosis was detected after 3 hours of incubation); (2) Taurine could apparently inhibit H(2)O(2)-induced bovine lens epithelial cell apoptosis. CONCLUSION: Taurine has an inhibitory role on H(2)O(2)-induced bovine lens epithelial cell apoptosis and can delay and ameliorate the occurrence and development of cataract.

61. Invest Ophthalmol Vis Sci. 1999 Mar;40(3):680-8. (Animal Study)

Effect of dietary taurine supplementation on GSH and NAD(P)-redox status, lipid peroxidation, and energy metabolism in diabetic precataractous lens.

Obrosova IG, Stevens MJ.

Department of Internal Medicine, University of Michigan Medical Center, Ann Arbor, USA.

PURPOSE: To evaluate changes in glutathione and NAD(P)-redox status, taurine and malondialdehyde (MDA) levels, glucose utilization, and energy metabolism in diabetic precataractous lenses and to assess whether these changes can be prevented with dietary taurine supplementation. METHODS: The experimental groups included control and streptozotocin-diabetic rats with a 3-week duration of diabetes fed unsupplemented or taurine (1% or 5%)-supplemented diets. The levels of glucose, sorbitol, fructose, myo-inositol, oxidized glutathione (GSSG), glycolytic intermediates, malate, alpha-glycerophosphate, and adenine nucleotides were assayed in individual lenses spectrofluorometrically by enzymatic methods, reduced glutathione (GSH) spectrofluorometrically with O-phthaldialdehyde, MDA colorimetrically with N-methyl-2-phenylindole, and taurine by high-performance liquid chromatography. Free cytosolic NAD+/NADH and NADP+/NADPH ratios were calculated from the lactate dehydrogenase and malic enzyme systems. RESULTS: Sorbitol pathway metabolites and MDA were increased, and GSH and taurine levels were reduced in diabetic rats versus controls. The profile of glycolytic intermediates (an increase in glucose 6-phosphate, no change in fructose 6-phosphate and fructose 1,6-diphosphate, an increase in dihydroxyacetone phosphate, a decrease in 3-phosphoglycerate, phosphoenolpyruvate, and pyruvate, and no change in lactate), and a 9.2-fold increase in alpha-glycerophosphate suggest diabetes-induced inhibition of glycolysis. Free cytosolic NAD+/NADH ratios, ATP levels, ATP/ADP, and adenylate charge were reduced, whereas free cytosolic NADP+/NADPH ratios were elevated. Lens taurine levels in diabetic rats were not affected by supplementation with 1% taurine. With 5% taurine supplementation, they were increased approximately 2.2-fold higher than those in untreated diabetics but remained 3.4-fold lower than in controls. Lens GSH levels were similar in diabetic rats fed unsupplemented and 5% taurine-supplemented diets, whereas GSSG and MDA levels and GSSG/GSH ratios were reduced by 5% taurine supplementation. The decrease in free cytosolic NAD+/NADH, ATP/ADP, and adenylate energy charge were ameliorated by 5% taurine supplementation, whereas accumulation of sorbitol pathway intermediates, depletion of myoinositol, inhibition of glycolysis, a decrease in ATP and total adenine nucleotide, and an increase in free cytosolic NADP+/NADPH were not prevented. CONCLUSIONS: Dietary taurine supplementation ameliorates MDA levels, GSSG/GSH, and NAD+/NADH and fails to prevent the osmotically mediated depletion of GSH and taurine and the decrease in glucose utilization and ATP levels in diabetic precataractous lens. Dietary taurine supplementation cannot be regarded as an alternative to aldose reductase inhibition in eliminating antioxidant and metabolic deficits contributing to diabetes-associated cataractogenesis.

62. Free Radic Res. 1998 Sep;29(3):189-95. (Animal Study)

Oxidative stress to rat lens in vitro: protection by taurine.

Devamanoharan PS, Ali AH, Varma SD.

Department of Ophthalmology, University of Maryland, Baltimore 21201, USA.

The concentration of taurine is high in the lens. However, its function therein remains unknown. Studies from other tissues suggest that in addition to several other modes of action, it acts as an antioxidant. We therefore hypothesize that taurine may be a part of the antioxidant defense mechanisms involved in protecting the lens against oxidative stress and consequent cataract formation. In these studies, the protective effect of taurine was examined using lens culture system with menadione as an oxidant. Inclusion of this compound in the incubation medium was found to have several adverse effects on the lens, such as a decrease in its ability to accumulate rubidium against a concentration gradient and fall in the levels of glutathione, ATP and an increase in water insoluble proteins. All these deleterious effects were attenuated significantly by addition of physiological amounts of taurine to the menadione-containing medium.

63. Mol Cell Biochem. 1997 Dec;177(1-2):245-50.

Prevention of lens protein glycation by taurine.

Devamanoharan PS, Ali AH, Varma SD.

Department of Ophthalmology, University of Maryland School of Medicine, Baltimore 21201, USA.

Modifications in lens protein structure and function due to nonenzymic glycosylation and oxidation have been suggested to play a significant role in the pathogenesis of sugar and senile cataracts. The glycation reaction involves an initial Schiff base formation between the protein NH2 groups and the carbonyl group of a reducing sugar. The Schiff base then undergoes several structural modifications, via some oxidative reactions involving oxygen free radicals. Hence certain endogenous tissue components that may inhibit the formation of protein-sugar adduct formation may have a sparing effect against the cataractogenic effects of sugars and reactive oxygen. The eye lens is endowed with significant concentration of taurine, a sulfonated amino acid, and its precursor hypotaurine. It is hypothesized that taurine and hypotaurine may have this purported function of protecting the lens proteins against glycation and subsequent denaturation, in addition to their other functions. The results presented herein suggest that these compounds are indeed capable of protecting glycation competitively by forming Schiff bases with sugar carbonyls, and thereby preventing the glycation of lens proteins per se. In addition, they appear to prevent oxidative damage by scavenging hydroxyl radicals. This was apparent by their preventive effect against the formation of the thiobarbituric acid reactive material generated from deoxy-ribose, when the later was exposed to hydroxyl radicals generated by the action of xanthine oxidase on hypoxanthine in presence of iron.

64. Invest Ophthalmol Vis Sci. 1993 Jul;34(8):2512-7.

Hypertonic stress increases NaK ATPase, taurine, and myoinositol in human lens and retinal pigment epithelial cultures.

Yokoyama T, Lin LR, Chakrapani B, Reddy VN.

Eye Research Institute, Oakland University, Rochester, Michigan.

PURPOSE. Recent evidence suggests that taurine and myoinositol may serve as organic osmolytes in a number of cells, including lens and retinal pigment epithelia, but the mechanism for their increased accumulation in response to hypertonic stress is not known. To assess whether NaK ATPase contributed to the elevated levels of taurine and myoinositol in cells exposed to hypertonic media, we measured the activity of NaK ATPase, which is known to be implicated in the transport of these substances, in human lens and retinal pigment epithelia cultured in isotonic and hypertonic media. METHODS. Primary cultures of human lens epithelial (HLE) and human retinal pigment epithelial (HRPE) cells were maintained in isotonic and hypertonic media for varying periods of time, and the activity of NaK ATPase and the levels of taurine and myoinositol were measured in cells cultured under two different conditions. The possible involvement of the transport enzyme in the accumulation of the two osmolytes was also investigated by inhibiting the enzyme with ouabain. RESULTS. When primary cultures of HLE and HRPE were exposed to hypertonic medium containing NaCl (600 mOsm) or cellobiose (500m Osm) for 72 hours, the concentration of taurine and myoinositol in HLE cells increased by 218% and 558% of control, respectively, in NaCl medium, whereas the corresponding increases in cellobiose medium were 147% and 439%. In HRPE cells, the increase in myoinositol levels in the two hypertonic media was more dramatic than that in taurine. Concomitant with the increase in the concentration of the osmolytes, there was an increase in NaK ATPase activity in both cell types. Although the accumulation of taurine in HLE cells in hypertonic media in a 6-hour culture was essentially prevented by 10(-8) mmol/l ouabain, myoinositol levels were affected to a lesser, but still significant, extent. In HRPE cells, which were cultured for 24 hrs in the presence of 10(-6) mmol/l ouabain, there was a more direct correlation between the inhibition of NaK ATPase and the decreased accumulation of taurine and myoinositol in the hypertonic media. CONCLUSION. Although the exact mechanism by which NaK ATPase activity increases in response to hypertonic stress remains to be established, the increased activity of the enzyme is related to the enhanced accumulation of the organic osmolytes, taurine, and myoinositol, in HLE and HRPE cells cultured in hypertonic medium.

65. Neurochem Res. 1986 Apr;11(4):535-42. (Animal Study)

Taurine and other free amino acids in the retina, vitreous, lens, iris-ciliary body, and cornea of the rat eye.

Heinamaki AA, Muhonen AS, Piha RS.

Levels of free amino acids were determined quantitatively in whole ocular tissues of the rat eye with aid of a sensitive amino acid analyzer. The tissues studied were the retina, vitreous, lens, iris-ciliary body, and cornea. The retina and lens contained a more concentrated free amino acid pool than other tissues. The neuroactive amino acids taurine. GABA, glutamic acid, aspartic acid, and glycine were clearly enriched in the retina. Taurine was the most abundant amino acid in all five tissues studied, and its high concentration in non-neural tissues, especially the lens, suggests that it must have other functions as well as neurotransmitter ones in the rat eye.

66. Exp Eye Res. 1983 Oct;37(4):379-84.

Distribution of taurine in the crystalline lens of vertebrate species and in cataractogenesis.

Gupta K, Mathur RL.

Marked heterogeneity was observed in the distribution of taurine in different regions of the lens in various species. In general low taurine pools were observed in the nucleus of all species except frog and human. The distribution of taurine in human senile cataractous lenses at different stages of maturation showed decreased contents in all the regions except capsule epithelium as compared to the normal human lenses. This decrease is progressive upto the 'mature' stage of cataract. In rat lenses with galactose cataracts taurine contents decreased by about 83-94% of the normal values in the equatorial, anterior, posterior cortical and nuclear regions.

Cardiac Lesions

67. Can J Neurol Sci. 1980 Nov;7(4):435-40. (Animal Study)

Taurine decreases lesion severity in the hearts of cardiomyopathic hamsters.

Azari J, Brumbaugh P, Barbeau A, Huxtable R.

Cardiomyopathic Syrian hamsters develop necrotic lesions consequent upon calcium overload from 60 days of age onward. Taurine, given as a 0.1 M solution in place of drinking water for one month prior to sacrifice of animals of initial age 35 days, decreased the severity of subsequently developing cardiac lesions by 40%. Calcium concentration in the heart was decreased by 57%. Magnesium and iron concentrations were unaltered. Taurine given in a similar manner for 4 months had a protective effect, decreasing lesion severity by 21% and calcium concentration by 35%. Magnesium concentrations were increased by 12%. Compared to random-bred animals, cardiomyopathic hamsters at one and two months of age have the same concentrations of calcium, magnesium and iron in the quadrants of the heart, except in the left ventricle, which has significantly higher concentration of calcium. Calcium concentrations are 70%, 1320% and 2100% higher respectively in one month, two month and five month old animals. Five month old animals differ slightly but significantly in iron (17% decrease) and magnesium concentrations (17% increase). Cardiomyopathic hamsters have insignificant differences in beta-adrenergic receptor density compared to random-bred animals and have a significantly higher rate of taurine influx.

Cardiovascular Effects

68. Gen Pharmacol. 1998 Apr;30(4):451-63.

Review of some actions of taurine on ion channels of cardiac muscle cells and others.

Satoh H, Sperelakis N.

Department of Pharmacology, Nara Medical University, Japan.

1. Taurine has recently been known to protect against ischemia and heart failure. Taurine possesses plenty of actions on the ion channels and transports, but is very non-specific. 2. Taurine may directly and indirectly help to regulate the [Ca]i level by modulating the activity of the voltage-dependent Ca2+ channels (also dependent on [Ca]i/[Ca]o), by regulation of Na+ channels, and secondly via Na-Ca exchange and Na(+)-taurine cotransport. 3. Taurine can prevent the Ca2+ ([Ca]o or [Ca]i)-induced cardiac functions. 4. Therefore, it seems possible that taurine could exert the potent cardioprotective actions even under the condition of low [Ca]i levels as well as under the Ca2+ overload condition. 5. The electrophysiological actions of taurine on cardiomyocytes, smooth muscle cells, and neurons from recent studies are summarized.

69. Arzneimittelforschung 1998 Apr;48(4):360-4 (Animal Study)

Protective effects of taurine against reperfusion-induced arrhythmias in isolated ischemic rat heart.

Chahine R, Feng J Laboratory of Physiology, Faculty of Medical Sciences, Lebanese University, Beirut, Lebanon.

The protective effect of taurine (CAS 107-35-7) against reperfusion-induced arrhythmias has been investigated in isolated perfused rat heart (Langendorff method). Partial ischemia was induced by occlusion of left descending artery for 15 min, followed by 10 min reperfusion. Left ventricular pressure and epicardial ECG were continuously monitored before and during ischemia and reperfusion. A control group was submitted to partial ischemia without taurine treatment. Three groups were submitted to partial ischemia, under taurine (10 mmol/l) treatment in the Krebs-Henseleit perfusing buffer during ischemia only (group 1), at reperfusion (group 2) and throughout the experimental period (group 3). Malondialdehyde levels were measured as an index of lipid peroxidation and heart muscle damage. The incidence of irreversible ventricular fibrillation was significantly diminished from 83% (control group) to 36% in group 1, 42% in group 2 and 16% in group 3. The incidence of premature ventricular beats and ventricular tachycardia at reperfusion as well as malondialdehyde levels were significantly decreased under taurine treatment. The results indicate that taurine protects ischemic heart against reperfusion-induced arrhythmias, via both its properties as membrane stabilizer and oxygen free radical scavenger.

70. Ann Acad Med Stetin. 1997;43:129-42. (Animal Study)

[Taurine as a regulator of fluid-electrolyte balance and arterial pressure]

[Article in Polish]

Ciechanowska B.

Z Katedry Chorob Dzieci Pomorskiej Akademii Medycznej w Szczecinie, Szczecin.

Taurine is a sulfonic beta-amino acid which occurs in the highest concentration in the brain, the retina and in the myocardium. In cardiomyocytes it presents about 50% of free amino acids and plays a role as an osmoregulator, an inotropic factor and has an antiarrhythmic property. Moreover, taurine lowers arterial pressure by extension of diuresis and by vasodilatation. Similar effect on the vascular system and arterial pressure is exerted by atrial natriuretic peptide (ANP). Increase of both ANP secretion and myocardial taurine concentration is present in the same diseases as congestive cardiac failure, hypertension and hypernatremia. The aim of the study was the evaluation of general taurine depletion, caused by making the rats drink guanidinoethyl sulfonate (GES)--an inhibitor of taurine transport affecting fluid balance and arterial pressure as well as plasma ANP concentration under normal conditions and after increase of sodium load. The 103 male Wistar rats weighing 250-300 g were used. The animals were separated into 5 groups. Control group received tap water to drink. Group II was sodium-loaded by drinking 171 mmol/l NaCl. In group III depletion of taurine was obtained by the intake of 60 mmol/l GES. Rats in group IV were drinking 60 mmol/l GES in 171 mmol/l NaCl. Group V was made to drink 200 mmol/l taurine in 171 mmol/l NaCl. All animals had standard food and were able at any time to drink. Duration of the experiment was 20 days. At the onset and after 10 and 20 days the rats were weighed and their systolic blood pressure was measured by tail plethysmography. After 10 and 20 days of the study, plasma and myocardium taurine concentration, ANP, hematocrit, plasma osmolity, natremia, kalemia, urea and creatinine concentrations were determined. Taking GES for 20 days led to 43% decrease of plasma taurine and its myocardium content about 50% as compared to control group (Tab. 2). High, statistically significant correlation (r = 0.50, p < 0.001) between myocardium taurine and plasma ANP was found. The animals with taurine depletion had significantly lower (about 30%) plasma ANP concentration (Tab. 3), higher natremia (Tab. 4) and their arterial pressure increased due to sodium load. Systolic pressure was 11 mm Hg higher in that group in comparison to control and other groups (Tab. 1). However, the sodium-loading of the rats that drank taurine solution led to an increase of hematocrit, plasma osmolity, urea concentration and body mass gain as compared to control group, but without any arterial pressure increase. The sodium-loaded rats with normal plasma and myocardium taurine concentration were affected in a similar manner. The rats with higher myocardium taurine concentration had lower heart mass index. Results of this work lead to the following conclusions: 1. Depletion of taurine in hearts of examined rats leads to a decrease of plasma atrial natriuretic peptide (ANP) concentration in plasma. 2. ANP secretion caused by salt loading is lower in animals with taurine depletion than in normal animals. 3. Sodium-loading of animals with taurine depletion leads to hypernatremia and to an increase of arterial pressure. 4. Addition of taurine to animals loaded with sodium may lead to their dehydration.

71. Am J Vet Res. 1992 Feb;53(2):237-41. (Animal Study)

Myocardial taurine concentrations in cats with cardiac disease and in healthy cats fed taurine-modified diets.

Fox PR, Sturman JA.

Department of Medicine, Animal Medical Center, New York, NY 10021.

Myocardial taurine concentrations were measured in cats with cardiac disease and in healthy cats fed diets with various concentrations of taurine. Group 1 was composed of 26 cats with 3 categories of naturally developing cardiac disease: dilatative cardiomyopathy (group 1A), 10 cats; hypertrophic cardiomyopathy (group 1B), 9 cats; and volume overload (group 1C), 7 cats. These cats had been fed various commercial diets. Group 2 was composed of 40 healthy cats that had been fed diets varying in taurine concentration (0 to 1% taurine) for at least 2 years. Mean myocardial taurine concentrations did not differ significantly between group-1 cats with dilatative cardiomyopathy and those with hypertrophic cardiomyopathy or volume overload. Cats in group 1A had a mean myocardial taurine concentration 3 times higher than healthy cats fed a taurine-free diet (P less than 0.002). Mean myocardial taurine concentrations did not differ significantly between group-1A cats and healthy cats fed a diet containing 0.02% taurine; group-1A cats had significantly lower mean myocardial taurine concentrations than did healthy cats fed a synthetic diet containing 0.05 or 1.0% taurine (P less than 0.001). Acute oral administration of taurine in 5 group-1A cats appeared to increase mean myocardial taurine concentrations, compared with similar cats not given taurine during treatment for cardiac failure. In group-2 cats, mean myocardial taurine concentrations increased directly with percentage of dietary taurine.

72. Eur J Pharmacol. 1986 May 13;124(1-2):129-33. (Animal Study)

Positive inotropic effect of some taurine-related compounds on guinea-pig ventricular strips perfused with low calcium medium.

Franconi F, Failli P, Stendardi I, Matucci R, Bennardini F, Baccaro C, Giotti A.

Taurine exerts a positive inotropic effect at a low calcium concentration. Of the compounds chemically related to taurine only L-cysteic and 2-aminobenzenesulfonic acid mimic taurine action. Their effect is concentration-dependent and not linked to the restoration of taurine tissue concentration in guinea-pig ventricular strips. Our data demonstrate that: (1) carbon chain length between amino and sulfonic groups is a crucial factor in the development of activity. (2) Substitution of the sulfonic group with other acid functions such as the substitution of the primary amino group or the introduction of the -COOH group onto the beta-carbon brings about a lack of activity.

73. Proc Soc Exp Biol Med. 1984 Oct;177(1):143-50. (Animal Study)

Taurine in hearts and bodies of embryonic through early postpartum CF1 mice.

Quilligan CJ, Hilton FK, Hilton MA.

The hearts and remaining bodies of embryonic and fetal mice of known gestational age and of neonatal mice up to the age of 8.5 days were freeze-dried, weighed, and analyzed for the amino acid, taurine, by high performance liquid chromatography. Although cardiac taurine is only a small fraction of the taurine in the rest of the body in all animals studied, the concentration of taurine in the heart is similar to that in the rest of the body (40-45 nmole/mg freeze-dried wt) in embryos through Day 14.5 of gestation. Cardiac taurine concentration then begins to exceed that of the remainder of the body which gradually declines throughout the period studied. A doubling of cardiac taurine concentration is seen at birth (Day 19.5) when the cardiac to body taurine ratio rises markedly and is maintained at 2-4 throughout the period of observation. A maximum concentration of cardiac taurine (110 nmole/mg freeze-dried wt) is recorded 2.5 days after birth. The dramatic increase in cardiac taurine concentration at the time of birth follows the reported appearance in neonatal mouse hearts of adult levels of beta-adrenergic receptors and the increased work load of the heart.

74. Eur J Pharmacol. 1984 Feb 17;98(2):269-73. (Animal Study)

TAG antagonises the central cardiovascular effects of taurine.

Bousquet P, Feldman J, Bloch R, Schwartz J.

The taurine antagonist TAG was examined for its blocking activity towards the central cardiovascular effects of taurine and muscimol. Intracerebroventricular (i.c.v.) injections of taurine (1-1000 micrograms/kg) and muscimol (0.1-3 micrograms/kg) in the anesthetised cat led to hypotension and bradycardia. Pretreatment with TAG (1 mg/kg i.c.v.) antagonised the blood pressure effects of taurine. The selectivity of this antagonism is discussed since TAG also shifted to the right the blood pressure dose-response curve obtained with muscimol.

75. Res Commun Chem Pathol Pharmacol. 1984 Feb;43(2):343-6. (Animal Study)

Further evidence of the antiarrhythmic efficacy of taurine in the rat heart.

Hernandez J, Artillo S, Serrano MI, Serrano JS.

The potential antidysrrhythmic effect of taurine has been studied both "in vitro" and "in vivo". "In vitro experiments were performed on a model of automaticity induced in the isolated right ventricle of the rat. The "in vivo" studies have been done on anesthetized rats, assessing the effect of taurine on the electrical activity of the heart by continuous ECG records. Taurine decreases the "in vitro" automatic ventricular frequency. "In vivo" reduces heart rate (P-P interval increases) and conduction through the ventricular myocardium (prolongs QRS interval duration). We conclude that taurine possesses experimentally antidysrrhythmic activity "in vitro" and "in vivo", that would warrant further research.

76. Life Sci. 1983 Oct 24;33(17):1649-55. (Animal Study)

Effects of taurine and a taurine antagonist on some respiratory and cardiovascular parameters.

Wessberg P, Hedner T, Hedner J, Jonason J.

Respiratory performance, heart rate and blood pressure were studied in halothane anesthetized rats after administration of taurine and the putative taurine antagonist 6-aminomethyl-3-methyl-4H-1,2,4-benzothiadiazine-1, 1-dioxide hydrochloride (TAG). Intracerebroventricular (i.c.v.) taurine depressed ventilation due to decreased inspiratory neural drive and depression of respiratory timing mechanisms. I.c.v. administration of 1-100 micrograms TAG caused no changes in the respiratory and circulatory parameters studied except at the highest dose interval where respiratory frequency and minute ventilation were depressed. The respiratory depression induced by taurine (0.2 mg) or beta-alanine (1 mg) was antagonized by administration of TAG (100 micrograms). However, TAG did not antagonize the respiratory effects induced by i.c.v. glycine or gamma-aminobutyric acid (GABA) in equipotent respiratory depressant doses. The decline in inspiratory neural drive as well as in "respiratory timing" after i.c.v. taurine was restituted toward control values by TAG. The hypotension and bradycardia induced by taurine were also antagonized by TAG. It is concluded that TAG seems to antagonize the depressant action of taurine and beta-alanine but not of GABA and glycine on respiratory performance. TAG might also possess some partial agonist activity in higher doses.

77. Cardiovasc Res. 1983 Oct;17(10):620-6. (Animal Study)

Protection by oral pretreatment with taurine against the negative inotropic effects of low-calcium medium on isolated perfused chick heart.

Sawamura A, Azuma J, Harada H, Hasegawa H, Ogura K, Sperelakis N, Kishimoto S.

Chicks were given taurine by mouth using a cannula pushed down into the oesophagus. This treatment had protected the heart, when subsequently removed, against the decline of contractile force in the perfused heart brought about by low-calcium media. A small but statistically significant increase in taurine concentration occurred in the ventricular tissue of such pretreated hearts. In contrast, pretreatment with taurine did not affect ventricular calcium level. Addition of taurine (3 to 100 mmol . litre-1) into the perfusing solution did not alter the cyclic AMP level in the control perfused hearts, and failed to induce slow channel action potentials in hearts whose fast Na+ channels had been inactivated by high K+ (25 mmol . litre-1). However, taurine perfusion produced a significant positive inotropic action which became stable after 5 to 10 min of exposure.

78. Med Biol. 1982 Dec;60(6):316-22. (Animal Study)

Cardiovascular and ventilatory effects of taurine and homotaurine in anaesthetized rats.

Paakkari P, Paakkari I, Karppanen H, Halmekoski J, Paasonen MK.

The cardiovascular and ventilatory effects of intravenous (i.v.) or intracerebroventricular (i.c.v.) injections of the aminosulphonic acids, taurine and homotaurine, were studied in urethane-anaesthetized rats. Taurine induced dose-dependent falls in blood pressure, heart rate and ventilatory tidal volume on i.c.v. but not on i.v. administration. Homotaurine induced dose-dependent hypotension and bradycardia when given i.v. and i.c.v. It was, however, more effective when injected i.c.v., and the decrease in ventilatory tidal volume occurred after i.c.v. administration of homotaurine only. Pretreatment of the rats with reserpine attenuated both the hypotensive and bradycardic responses to taurine and homotaurine. Atenolol and atropine both partly inhibited, and in combination totally abolished, the bradycardic effects of taurine and homotaurine without changing the hypotensive responses to these compounds. The ventilatory responses were not significantly changed by any of the pretreatments. The results suggest that the central cardiovascular effects of taurine and homotaurine are mediated both by a decrease in sympathetic tone and an increase in the parasympathetic tone.

79. Am J Clin Nutr. 1981 Feb;34(2):204-10. (Animal Study)

Bile lipid alterations in taurine-depleted monkeys.

Stephan ZF, Armstrong MJ, Hayes KC.

Newborn cebus and cynomolgus monkeys, differing in their inherent taurine-glycine conjugation of bile acids, were fed taurine-free soy protein infant formula (Isomil) with or without added taurine (500 mg/kg dry diet). After 5 months, monkeys were anesthetized, their enterohepatic circulation interrupted, and their bile pool drained for 4.5 h. Bile acid conjugation, total bile acid pool size, biliary lipid composition, and theoretical maximal cholesterol solubility in bile were determined. Taurine depletion in cebus monkey, an obligate taurine conjugator (97%), did not reduce bile acid conjugation with taurine, or did it alter bile acid pool size, biliary lipid composition, or theoretical maximal cholesterol solubility in bile. Conversely, taurine depletion in cynomolgus, a species normally conjugating with some glycine (15 to 20%), significantly reduced conjugation of taurine with bile acids from 84 to 64%, essentially doubling that of glycine from 16 to 36%. Furthermore, theoretical maximal cholesterol solubility in cynomolgus bile improved significantly as a result of taurine depletion. This improvement was associated with increased percentage distribution of biliary phospholipid from 17 to 33%, in turn reflecting an increase in the taurochenodeoxycholate to taurocholate ratio from 0.7 to 2.9. Concomitant increase in biliary cholesterol concentration associated with increased glycine conjugation precluded any changes in the percent saturation of bile which remained constant at 130% for both dietary groups of cynomolgus. Taurochenodeoxycholate uniquely conserved taurine in the face of body taurine depletion. Taurine availability thus potentially has a substantial influence on bile acid characteristics and cholesterol solubility in a glycine conjugating primate.

80. Recent Adv Stud Cardiac Struct Metab. 1976 May 26-29;12:259-63. (Animal Study)

Cardiac muscle taurine: effects of acute left ventricular ischemia in the dog and anoxic perfusion of the rat heart.

Crass MF 3rd, Song W, Lombardini JB.

It has been proposed that taurine, or one of its metabolites, may exert anti-arrhythmic effects in cardiac muscle. The present studies examined the effects of acute left ventricular ischemia in the dog (in vivo) and whole heart anoxia in the perfused rat heart (in vitro) on the content and distribution of taurine. In control dogs an increasing outer-to-inner gradient in taurine content was observed in the left ventricle. Left circumflex artery ligation for four hours markedly decreased tissue taurine content, the greatest disappearance occurring in the inner zone. Anoxic perfusion resulted in a similar decrease in rat ventricular taurine levels. Recovery of taurine in the heart perfusates indicated that tissue disappearance, secondary to oxygen deficiency, involved leakage into the extracellular fluid rather than metabolic conversion.

Cholestasis

81. Am J Clin Nutr. 1983 Feb;37(2):221-32.

Taurine prevents cholestasis induced by lithocholic acid sulfate in guinea pigs.

Dorvil NP, Yousef IM, Tuchweber B, Roy CC.

The hypothesis that the amino acid used for the conjugation of sulfolithocholate (S-LCA) is a critical determinant of its cholestatic potential was tested in the guinea pig which conjugates 90% of its bile acids with glycine. Twelve groups of animals were used to study the effect of taurine feeding at a concentration of 0.5% in the drinking water for periods of 1, 3, and 5 days before an iv injection of 18 mumol/100 g body weight of S-LCA. Bile flow was monitored in 30-min aliquots over a 3-h period and the bile acid secretion as well as the glycine/taurine ratio of conjugated bile acids were determined. At the end of the various time periods, the livers were examined by light and electron microscopy. Within 3 days after taurine administration there was an increase in bile flow and a reversal of the glycine/taurine ratio with taurine conjugates becoming predominant. Liver morphology was unchanged except for a slight accumulation of lipids after 5 days of taurine feeding. In animals who were not pretreated with taurine, S-LCA injection led to a progressive decrease in bile flow such, that it was reduced to less than 20% at the end of the 3-h collection. S-LCA was conjugated almost exclusively with glycine. In contrast, in the groups fed taurine for 1, 3, and 5 days before the S-LCA injection, bile flow was comparable to that of the groups fed taurine alone. The S-LCA recovered in bile was to a large extent conjugated with taurine. S-LCA animals pretreated with taurine did not exhibit any liver cell changes while the group which had not received taurine before the S-LCA injection showed numerous cytoplasmic vacuoles with normal bile canaliculi. These data show that increasing the availability of taurine through dietary means may exert a protective effect against cholestasis induced by monohydroxy bile acids.

Retinal Function

82. J Neurosci Res. 2003 Sep 1;73(5):731-6. (Animal Study)

Exogenous glutamate and taurine exert differential actions on light-induced release of two endogenous amino acids in isolated rat retina.

Barabas P, Kovacs I, Kardos J, Schousboe A.

Department of Neurochemistry, Institute of Chemistry, Chemical Research Center, Hungarian Academy of Sciences, Budapest, Hungary.

A dark-adapted isolated rat retina, preloaded with [(14)C]glutamate ([(14)C]Glu) and [(3)H]taurine ([(3)H]Tau), was superfused with artificial cerebrospinal fluid (ACSF) in the absence and presence of Glu (1 mM) or Tau (1 mM), as well as the Glu uptake inhibitors dihydrokainic acid (DHK, 0.04 mM) and trans-L-pyrrolidine-2,4-dicarboxylate (t-PDC, 0.004 mM). After 10 min of light stimulation, the extracellular level of [(14)C]Glu and [(3)H]Tau was reduced to 82 +/- 2% and 65 +/- 4% of the control, respectively. Basal release was enhanced when Tau and t-PDC were applied together, although none of the compounds had any effect when applied individually. Glu and DHK had no effect. The decrease of [(14)C]Glu efflux evoked by light stimuli was enhanced by t-PDC and Tau, either added separately or together, whereas Glu and DHK were without effect. In contrast, [(3)H]Tau efflux variations induced by light stimuli were reduced markedly by both Tau and Glu. These findings suggest distinctly different roles of Tau and Glu in light-induced responses in mammalian retina, including a possible role for Tau in light adaptation processes. Copyright 2003 Wiley-Liss, Inc.

83. Nutr Neurosci. 2003 Aug;6(4):253-61. (Animal Study)

Effects of taurine deficiency and chronic methanol administration on rat retina, optic nerve and brain amino acids and monoamines.

Gonzalez-Quevedo A, Obregon F, Urbina M, Rousso T, Lima L.

Instituto de Neurologia y Neurocirugia, Ciudad de la Habana, Cuba.

A chronic methanol (MeOH) intoxication scheme (2 g/kg/day ip for 2 weeks) was carried out in Sprague-Dawley rats, previously depleted of folates with methotrexate (MTX). beta-Alanine (beta-Ala), 5%, was also administered to some animals in the drinking water. Amino acids were determined in plasma, retina, optic nerve, hippocampus and posterior cortex by HPLC with fluorescence detection and monoamines in retina, hippocampus and posterior cortex by electrochemical detection. Beta-Ala administration reduced taurine (Tau) levels in plasma, hippocampus and posterior cortex, but not in retina and optic nerve. Aspartate (Asp) concentration in the optic nerve was increased in MTX-MeOH treated animals, and the administration of beta-Ala did not modify this elevation. The association of beta-Ala with MTX-MeOH produced an increase of threonine, and a decrease of 5-hydroxytryptamine (5-HT) in the retina without modifying 5-hydroxyindoleacetic acid, whereas in the hippocampus an elevation of asparagine was observed. We conclude that, in the retina, beta-Ala in combination with MTX-MeOH increased serotonin and decreased dopamine (DA) turnover rate, and resulted in changes in the amino acid balance, that could affect glycinergic activity. On the other hand, in the hippocampus, Asp metabolism could be affected by Tau depletion with beta-Ala.

84. Free Radic Res. 2003 Mar;37(3):323-30. (Animal Study)

Potential therapeutic effect of antioxidants in experimental diabetic retina: a comparison between chronic taurine and vitamin E plus selenium supplementations.

Di Leo MA, Ghirlanda G, Gentiloni Silveri N, Giardina B, Franconi F, Santini SA.

Department of Emergency Medicine, Catholic University, Roma, Italy.

Although good glycaemic control can delay the development and progression of diabetic retinopathy, new therapies are needed to obtain a better control of this diabetic complication. Oxidative stress seems to be a contributing factor in diabetic retinal alterations, therefore, it has been suggested that antioxidants may be beneficial in reducing diabetic retinal changes. However, many questions are still open. In fact, it remains to be ascertained which antioxidants are the most active when they are chronically administered in vivo and their effective dosages. Therefore, we compared the effect of chronic taurine supplementations versus a mixture of vitamin E + selenium on biochemical retinal changes induced by diabetes at different stages of the disease. Briefly, streptozotocin (STZ) diabetic rats were administered for 4 months following the dietary supplements: (a) 2% (w/w) taurine; (b) 5% (w/w) taurine; (c) 200 IU vitamin E + 8 mg selenium/kg diet (d) 500 IU vitamin E + 8 mg selenium/kg diet. In STZ diabetic rat in poor metabolic control (i.e. serum glucose >16.5 mmol/l), at 2, 4, 8, 16 weeks following the onset of diabetes, retinal conjugated dienes (CD) and lipid hydroperoxides (LP) were significantly and progressively increased, while sodium pump activity was gradually and significantly reduced. In taurine and vitamin E + selenium supplemented diabetic rats, glycaemia and body weight were not significantly different from those of non-supplemented diabetic animals. In diabetic rats, 2 and 5% taurine significantly decreased CD. This reduction is long lasting. Regarding CD, both vitamin E + selenium supplementations reduced CD only during the first 4 weeks of diabetes. Two percent taurine supplementation significantly lowered LP for the first 8 weeks of the disease while 5% taurine-induced-reduction lasted for the whole experimental time. A 200 IU vitamin E + 8 mg selenium supplementation did not significantly modify LP, while 500 IU vitamin E + 8 mg selenium significantly lowered them for the whole studied period. Finally, taurine preserved ATPase activity being more effective at 5% than 2%. Two hundred IU vitamin E + 8 mg selenium did not generally modify pump activity, while 500 IU vitamin E + 8 mg selenium partially prevented the decrease in pump activity. We conclude that taurine and vitamin E + selenium supplementations ameliorate biochemical retinal abnormalities caused by diabetes. These effects are dose- and time-dependent Moreover, the effect of taurine on CD is longer lasting than that of vitamin E + selenium. In addition, taurine seems to better preserve ATPase activity in comparison with vitamin E + selenium. Finally, in diabetic animals a negative correlation is found between CD and LP on one side and Na+K+ATPase activity on the other; thus, lipid peroxidation and pump activity seem to be associated. The same inverse correlations are present in vitamin E + selenium supplemented diabetic rats, but are lost in taurine supplemented animals. Therefore, taurine effects may not be simply mediated by its antioxidant activity. Thus, chronical (4 months) taurine and vitamin E + selenium supplementations reduce biochemical retinal alterations in diabetic rat in poor metabolic control.

85. Nutr Neurosci. 2002 Apr;5(2):75-90.

Taurine: evidence of physiological function in the retina.

Militante JD, Lombardini JB.

Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430, USA.

Taurine is a free amino acid found in high millimolar concentrations in mammalian tissue and is particularly abundant in the retina. Mammals synthesize taurine endogenously with varying abilities, with some species more dependent on dietary sources of taurine than others. Human children appear to be more dependent on dietary taurine than adults. Specifically, it has been established that visual dysfunction in both human and animal subjects results from taurine deficiency. Moreover, the deficiency is reversed with simple nutritional supplementation with taurine. The data suggest that taurine is an important neurochemical factor in the visual system. However, the exact function or functions of taurine in the retina are still unresolved despite continuing scientific study. Nevertheless, the importance of taurine in the retina is implied in the following experimental findings: (1) Taurine exhibits significant effects on biochemical systems in vitro. (2) The distribution of taurine is tightly regulated in the different retinal cell types through the development of the retina. (3) Taurine depletion results in significant retinal lesions. (4) Taurine release and uptake has been found to employ distinct regulatory mechanisms in the retina.

86. Glia. 2002 Feb;37(2):153-68. (Animal Study)

Localization of taurine transporters, taurine, and (3)H taurine accumulation in the rat retina, pituitary, and brain.

Pow DV, Sullivan R, Reye P, Hermanussen S.

Department of Physiology and Pharmacology, School of Biomedical Sciences, University of Queensland, Brisbane, Australia. d.pow@mailbox.uq.edu.au

The nervous system contains an abundance of taurine, a neuroactive sulfonic acid. Antibodies were generated against two cloned high-affinity taurine transporters, referred to in this study as TAUT-1 and TAUT-2. The distribution of such was compared with the distribution of taurine in the rat brain, pituitary, and retina. The cellular pattern of [(3)H] taurine uptake in brain slices, pituitary slices, and retinas was examined by autoradiography. TAUT-2 was predominantly associated with glial cells, including the Bergmann glial cells of the cerebellum and astrocytes in brain areas such as hippocampus. Low-level labeling for TAUT-2 was also observed in some neurones such as CA1 pyramidal cells. TAUT-1 distribution was more limited; in the posterior pituitary TAUT-1 was associated with the pituicytes but was absent from glial cells in the intermediate and anterior lobes. Conversely, in the brain TAUT-1 was associated with cerebellar Purkinje cells and, in the retina, with photoreceptors and bipolar cells. Our data suggest that intracellular taurine levels in glial cells and neurons may be regulated in part by specific high-affinity taurine transporters. The heterogeneous distribution of taurine and its transporters in the brain does not reconcile well with the possibility that taurine acts solely as a ubiquitous osmolyte in nervous tissues. Copyright 2002 Wiley-Liss, Inc.

87. Zhongguo Ying Yong Sheng Li Xue Za Zhi. 2000 Nov;16(4):343-6.

[Influences of taurine and micronutrients on nitric oxide synthase expression and cGMP content in rat retina]

[Article in Chinese]

Mi MT, Zhu JD, Wei N, Shi YG, Huang GR.

Department of Nutrition and Hygiene, Third Military Medical University, Chongqing 400038.

AIM: To investigate the influence of taurine and micronutrients on visual signal transmission. METHODS: Wistar rats were divided into three groups, that is control group, experiment group 1 and experiment group 2, and fed for 3 weeks with normal diet, 5 times and 10 times doses of requirements of taurine, vitamin A, vitamin B, zinc and selenium, then each treatment group were divided into light group and dark adaptation group. After feeding another 3 days in different environments with normal diet, all animals were killed and cGMP level and NOS expression were analysed in retina and retinogeniculate. RESULTS: The NOS expression and cGMP contents of photoreceptor cells, visual cortex and retinogeniculate were increased in dark adaptation group compared with light group. Nutritional intervention could enhance the NOS staining in dark environment, increased the cGMP contents whether light or dark condition. CONCLUSION: The distribution, expression and content of NO and cGMP are quite different in various light adaptation status. Taurine and micronutrient intervention may modurate the visual signal transmission or vision function mediated by the changes of NO or cGMP.

88. Adv Exp Med Biol. 2000;483:441-51.

Effects of osmotic and light stimulation on 3H-taurine efflux from isolated rod outer segments and synthesis of tauret in the frog retina.

Petrosian AM, Haroutounian JE, Fugelli K, Kanli H.

Buniatian Inst. of Biochemistry of Natl. Acad. Sci. of Armenia, Yerevan.

After injection of 3H-taurine into eyeballs of frogs and maintenance for 3 h in darkness by a gentle shaking, an almost homogenous fraction of rod outer segments (ROS) was prepared. About a 22% decrease in tonicity caused by reducing NaCl in isotonic 225 mOsm normal solution caused a rapid increase in the rate coefficient of efflux of 3H-taurine from the ROS fraction. The peak level of increased efflux rate coefficient was 7-times higher than the basal isotonic level. This indicates that taurine could contribute essentially to the volume regulation, either via selective channels or a carrier transporter-mediated pathways. For further clarifying if taurine fluxes in the ROS are sensitive to the light, other experiments were performed. Neither light stimulation of dark-adapted ROSs fractions or dark stimulation of weakly illuminated ROSs revealed any detectable changes in the efflux rate coefficient of 3H-taurine. These results indicate that light-induced taurine efflux, if present in the ROS, must be small, compared with hypoosmotic induced efflux. Thus the question of light-induced release of taurine from ROS still remains to be clarified. In the second part of this study, using TLC (thin layer chromatography) in combination with 3H-taurine measurements we have tried to clarify whether frogs (Rana ridibunda) eye structures can synthesize tauret (retinylidenetaurine). In isolated retinal preparations almost no any noticeable radioactivity was detected compared with background level. The capability of the eye structures to synthesize tauret from 3H-taurine was revealed in the second whole eye injection experiment. About 0.3% of the total 3H-taurine pool taken up was converted into 3H-tauret in the dark-adapted frog retina. In the retina of frogs adapted to light compared with those which were dark adapted tauret quantities were remarkable lower--on average about half. These results are in agreement with our recent data obtained by HPLC, which indicate tauret levels several times higher in the dark-adapted frog retinae compared with those after long lasting light adaption. Taking into account these results one can conclude that the main structure able to synthesize 3H-tauret is probably pigment epithelium rather than retina.

89. Neurochem Res. 1999 Nov;24(11):1333-8.

Taurine and its trophic effects in the retina.

Lima L.

Laboratorio de Neuroquimica, Centro de Biofisica y Bioquimica, Instituto Venezolano de Investigaciones Cientificas, Caracas. llima@cbb.ivic.ve

The sulphur amino acid taurine possesses variable functions during development and regeneration of the central nervous system. The retina synthesize and uptake taurine, which is the amino acid present in the highest concentration in this tissue. Deficiency of taurine alters the structure and the function of the cerebral and cerebellar cortex, as well as the retina. Taurine increases outgrowth of postcrush goldfish retina in culture, partially by elevating calcium influx, and also by the modulation of protein phosphorylation. Its concentration increases in the retina after the lesion of the optic nerve, and the intraocular injection of it, between the crush and the explantation, stimulates the outgrowth of neurites. Taken together, although there are a great number of unresolved questions on the mechanisms of action of this amino acid as a trophic substance, the results support the role of taurine during regeneration of the optic nerve.

90. Neurochem Int. 1999 Oct;35(4):301-6. (Animal Study)

Insulin-stimulated taurine uptake in rat retina and retinal pigment epithelium.

Salceda R.

Departamento de Neurociencias, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, D.F., Mexico. rsalceda@ifisiol.unam.mx

Taurine is found at millimolar concentration in the retina and retinal pigment epithelium. High concentrations of taurine are essential for maintenance of retinal function. Taurine uptake by retina and retinal pigment epithelium was significantly enhanced by physiological concentrations of insulin as well as by high glucose concentrations. The results indicate that both, glucose and insulin enhanced taurine uptake occur through an increase in transport capacity which offset an additional, small decrease in affinity of the taurine carrier. Similar results were observed in retina and retinal pigment epithelium from streptozotocin-induced diabetic rats, suggesting that glucose and insulin regulate the taurine carrier through the same mechanism.

91. Brain Res Brain Res Rev. 1991 May-Aug;16(2):151-69.

Taurine: retinal function.

Lombardini JB.

Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430.

The status and potential functions of taurine in the retina have been reviewed. Taurine is present in high concentrations in the retina of all species tested, while the retinal concentrations of the enzymes necessary to synthesize taurine are presumed to vary among those species. The documented low activity of cysteinesulfinic acid decarboxylase, a key enzyme in taurine biosynthesis, in the livers of the cat, monkey and human possibly reflect low activity in their retinas, indicating reliance on the diet as an important source of taurine. Both high- and low-affinity binding proteins and uptake systems have been described for taurine in retinal tissue. Evoked release of taurine by light and other depolarizing stimuli have been well documented. Retinal pathologies including diminished ERGs and morphologic changes have been reported for animals and man deficient in taurine. Possible functions for taurine in the retina include: (1) protection of the photoreceptor - based on the shielding effects of taurine on rod outer segments exposed to light and chemicals; (2), regulation of Ca2+ transport - based on the modulatory effects of taurine on Ca2+ fluxes in the presence and absence of ATP; and (3) regulation of signal transduction - based on the inhibitory effects of taurine on protein phosphorylation.

92. Mol Pharmacol. 1989 Aug;36(2):256-64. (Animal Study)

Analogues of taurine as stimulators and inhibitors of ATP-dependent calcium ion uptake in rat retina: combination kinetics.

Lombardini JB, Liebowitz SM, Chou TC.

Department of Pharmacology, Texas Tech University Health Sciences Center, Lubbock 79430.

Taurine is an amino acid that plays important roles in maintaining both the structural integrity and function of the retina. Thus, the effects of taurine, taurine analogues, and their combinations were studied in the ATP-dependent calcium ion uptake system at low calcium ion concentrations (10 microM) in a rat retinal membrane preparation. (+/-)-(trans)-2-Aminocyclopentanesulfonic acid (TAPS), a cyclic taurine analogue previously determined to inhibit ATP-dependent calcium ion uptake was demonstrated to be noncompetitive (Ki = 0.055 mM) with respect to taurine, that is, the values for the half-saturation concentrations calculated from varying concentrations of taurine compared with varying concentrations of taurine in the presence of a fixed concentration of TAPS (80 microM) did not change. However, the values for the maximal rates of change were significantly different. 1,2,3,4-Tetrahydroquinoline-8-sulfonic acid (THQS), a less potent inhibitor of ATP-dependent calcium ion uptake than TAPS, was also shown to be noncompetitive with taurine, with an inhibition constant (Ki) of 23.8 mM. Thus, it is presumed that both compounds (TAPS and THQS) are acting at receptor site(s) other than the taurine binding site. When TAPS and THQS were tested in a mixture that maintains a ratio (fixed ratio mixture) of 1 part TAPS and 25 parts THQS (by concentration, in mM), varied over a wide range of concentrations, and were then analyzed by median-effect plots and equation, the inhibitory effects are strongly synergistic, as shown by the combination index and the dose-reduction index. The parallel nature of the median-effect plots of TAPS and THQS indicates that the two inhibitors have a similar mode of action, that is, mutually exclusive. (+/-)-3-Aminotetrahydrothiophene-1,1-dioxide (ATS) and (+/-)-piperidine-3-sulfonic acid (PSA) are an agonist and partial agonist that demonstrated stimulatory effects on ATP-dependent calcium ion uptake. When tested in combination (1:1) with taurine, they were also determined to be mutually exclusive. It was demonstrated that ATS and taurine induced the same maximal rates of change of calcium ion uptake; however, PSA was less potent than taurine. The combination of taurine plus ATS was additive, whereas the combination of taurine plus PSA was synergistic. Structure-activity relationships of the taurine analogues and their topological relationships are discussed.

93. Vis Neurosci. 1989 Jul;3(1):33-8. (Animal Study)

Effects of dark maintenance on retinal biochemistry and function during taurine depletion in the adult rat.

Cocker SE, Lake N.

Department of Physiology, McGill University, Canada.

Light dependence of the effects of taurine depletion on retinal function and biochemistry was examined in albino rats housed either in cyclic lighting or in continuous darkness. Measurements of retinal taurine, DNA, and rhodopsin contents, and electroretinogram amplitudes were made at weekly intervals. Naka-Rushton parameters were estimated for the b wave amplitude-intensity function. No significant effects of lighting regime were observed on retinal taurine levels in untreated rats, or on the time course or extent of taurine depletion in animals treated with guanidinoethyl sulfonate, an antagonist of taurine transport. In both lighting schemes, treatment led to a linear reduction of retinal taurine content which plateaued after 5-6 weeks at 50% of control despite continued treatment. DNA values did not differ among groups, whereas rhodopsin levels doubled in both groups of dark-maintained rats. For treated rats housed in cyclic lighting, the onset of electroretinogram deficits paralleled the loss of retinal taurine in the absence of changes in rhodopsin levels or cell death. Vmax was significantly reduced after 4 weeks of treatment. In contrast, for rats housed in continuous darkness, there were no significant differences in electroretinogram parameters between control and taurine-depleted rats until after 10-14 weeks of treatment. This implies that light exposure accelerates the appearance of functional changes associated with retinal taurine deficiency. The basis of the light dependence and the interpretation of related studies is discussed.

94. J Neurosci Res. 1986;15(3):383-91. (Animal Study)

Pharmacological identification of retinal cells releasing taurine by light stimulation.

Salazar P, Quesada O, Campomanes MA, Moran J, Pasantes-Morales H.

The effect of drugs blocking synaptic activity at different retinal levels was examined in this study, in an attempt to identify the origin of the light-stimulated release of 3H-taurine from the chick retina. It was determined by autoradiography that the chick retina accumulates taurine in photoreceptors, in cells from the inner nuclear layer, and in processes of the inner plexiform layer. All these are possible sites for the release of taurine upon illumination. To discriminate among these possibilities, the effects of aspartate, tetrodotoxin, strychnine, picrotoxin, chlorpromazine, tubocurarine, atropine, glutamate diethyl esther, alpha-amino adipate and 2-amino-4-phosphonobutyrate were studied. Aspartate (10 mM), which is known to eliminate the light response of cells postsynaptic to photoreceptors, induced a marked increase of 150% in the resting efflux of 3H-taurine but did not decrease significantly the light-stimulated release. Tetrodotoxin, which blocks amacrine cell responses, decreased 3H-taurine release stimulated by light by less than 20%. The efflux of taurine was unaffected by strychnine, picrotoxin, tubocurarine, atropine, chlorpromazine, and 2-amino-4-phosphonobutyrate, whereas it was increased by glutamate diethyl esther and alpha-amino adipate. These results, all together, point to photoreceptors as the cells releasing 3H-taurine in response to light.

95. J Neurosci Res. 1982;8(4):631-42. (Animal Study)

Uptake, release, and binding of taurine in degenerated rat retinas.

Salceda R, Pasantes-Morales H.

High-affinity uptake, potassium-stimulated release and receptor binding of gamma-aminobutyric acid (GABA) and taurine were studied in retinas of rats treated with monosodium glutamate (MSG) or iodoacetate-malate (IAM). Such treatments produce a selective damage of the inner retinal layers (MSG) or of the photoreceptor layer (IAM). MSG treatment decreased GABA uptake by more than 60%. Also, the potassium-stimulated release of this amino acid was markedly diminished (90%) in retinas lesioned by MSG. MSG treatment decreased 3H-GABA binding by 45%. Uptake, release or binding of GABA were unaffected by IAM-treatment. Taurine uptake was reduced by a similar degree by both MSG and IAM treatment, 57% and 38% respectively. Potassium-stimulated release of taurine was unchanged by MSG and 50% reduced by IAM. Both treatments reduced the spontaneous release of endogenous taurine. Binding of taurine to receptors in retinal membranes was practically unaffected by any of the treatments utilized. These results are consistent with a neurotransmitter action of GABA at the inner retinal layers, while they do not support a major role for taurine as a synaptic transmitter in retina.

96. J Neurosci Res. 1981;6(4):497-509.

Alteration of metabolism of retinal taurine following prolonged light and dark adaptation: a quantitative comparison with gamma-aminobutyric acid (GABA).

Ida S, Nishimura C, Ueno E, Kuriyama K.

Alteration of metabolism of taurine in prolonged light- and dark-adapted frog retinae were studied in comparison with that of gamma-aminobutyric acid (GABA) and the following results were obtained. (1) Statistically significant alterations in retinal taurine, an increase in dark-adapted, and a decrease in light-adapted states, respectively, occurred when frogs were adapted continuously to light or dark for more than 3 weeks. Under the same experimental conditions, no alteration in retinal GABA was noted. (2) At 3 weeks and thereafter, a significant increase of retinal cysteine sulfinic acid decarboxylase (CSD; EC 4.1.1.12) activity, an enzyme involved in the biosynthetic pathway of taurine, also occurred in the dark, whereas the activity in the light-adapted retina was reduced. On the other hand, the retinal activity of L-glutamate decarboxylase (GAD; EC 1.1.1.15), the rate-limiting enzyme of GABA biosynthesis, was not altered in dark- as well as light-adapted state. Similarly, retinal GABA-transaminase (GABA-T; EC 2.6.1.19)-succinic semialdehyde dehydrogenase (SSADH; EC 1.2.1.16) was unaltered. (3) These alterations in retinal taurine were, however, unaccompanied by any changes in factors related to transmitter actions such as evoked release, high affinity uptake, and specific binding to synaptic membranes. The above results suggest that, different from GABA as a potent candidate for inhibitory neurotransmitter, retinal taurine may act as neuromodulator and/or may play an important role as a basic factor for maintaining cellular integrity under certain pathophysiological conditions.

Adrenal Gland

97. Jpn J Pharmacol. 1975 Dec;25(6):737-46.

Effect of taurine on alteration in adrenal functions induced by stress.

Nakagawa K, Kuriyama K.

When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following alpha-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-beta-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likly involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules.

Deficiency

98. Arch Neurol. 1975 Feb;32(2):108-13.

Hereditary mental depression and Parkinsonism with taurine deficiency.

Perry TL, Bratty PJ, Hansen S, Kennedy J, Urquhart N, Dolman CL.

An unusual neuropsychiatric disorder inherited in autosomal dominant fashion occurred in three successive generations of a family. Symptoms commenced late in the fifth decade in six affected patients and led to death in four to six years. The earliest and most prominent symptom was mental depression not responsive to antidepressant drugs or electroconvulsive therapy. This was accompanied by exhaustion, sleep disturbances, and marked weight loss. Later in the disease, symptoms of parkinsonism appeared, and respiratory failure occured terminally. The most recently affected family member was investigated biochemically late in his illness. Concentrations of taurine were greatly diminished in plasma and cerebrospinal fluid, and at autopsy, all regions of brain examined had a markedly reduced taurine content. Since taurine is a putative inhibitory synaptic transmitter, deficiency of brain taurine may possibly have caused the psychiatric and neurological manifestations of this disorder.

Cholesterol

99. J Lipid Res. 1984 May;25(5):448-55.

Effects of four taurine-conjugated bile acids on mucosal uptake and lymphatic absorption of cholesterol in the rat.

Watt SM, Simmonds WJ.

The importance of the bile acid structure on mucosal uptake and lymphatic absorption of cholesterol was investigated using four different taurine-conjugated bile acids. Pure synthetic conjugates of a trihydroxy bile acid, taurocholate, and three dihydroxy bile acids, tauroursodeoxycholate, taurochenodeoxycholate, and taurodeoxycholate were used to completely solubilize [14C]cholesterol and polar lipids for steady rate intraduodenal infusion for 8 hr in bile fistula rats. Lymph output and esterification of [14C]cholesterol and endogenous cholesterol were measured in hourly samples. A second group of bile fistula rats was given the same bile acids as the first group but without added cholesterol or other lipid, i.e., fasting lymph fistula group. Mucosal uptake of [14C]cholesterol was studied using recovery of [14C]cholesterol from lumen and mucosa after 1-hr infusions in conscious bile fistula rats. Lymph output of [14C]cholesterol was promoted more rapidly with taurocholate than with the dihydroxy conjugates and [14C]cholesterol output differed for the three groups given dihydroxy bile acids. The mass of cholesterol in lymph, measured chemically, varied in parallel with [14C]cholesterol absorption. For fasting lymph, infusion of dihydroxy bile acids failed to produce a significant change in endogenous cholesterol output when compared with rats given saline only. Taurocholate infusion markedly increased endogenous cholesterol in lymph of fasted rats. Under all conditions where cholesterol output was stimulated, the increase could be accounted for mainly as esterified cholesterol. Mucosal uptake of [14C]cholesterol during 1-hr infusions in conscious bile fistula rats was slower with the dihydroxy bile acids than with taurocholate. The results indicate the marked effect of the number and configuration of the hydroxyl groups on the solubilizing bile acid for cholesterol absorption.