Life Extension is a global authority on health, wellness and nutrition

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 ne