Anti-Aging News, January 1982 Vo.2, No. 1 pg 6-7
Cysteine is a strong reducing agent (it can prevent oxidation of some other substances). In fact, it has been found that too much cysteine in a cell culture medium can inactivate the hormone insulin contained in the medium. The insulin molecule contains three disulfide bonds, at least one of which can be reduced by cysteine. When this happens, the insulin molecule can no longer maintain the proper shape to function normally in stimulating the metabolism of sugar. In hypoglycemia attacks, there is too much insulin and too little sugar in the blood stream. Cysteine can inactivate insulin, thereby allowing the sugar level to begin to rise again. We and others have used the combination of vitamins B1, C, and cysteine to successfully abort severe attacks of hypoglycemia. A reasonable dose for a healthy adult is 5 grams of C, 1 gram of B1, and 1 gram cysteine. Although cysteine is a nutrient, it s use on a long-term basis should be considered experimental. Start with a low dose (250 milligrams per day) and work your way up. Always use at least three times as much vitamin C as cysteine. Be sure to consult with your physician and have regular clinical tests of basic body functions, especially liver and kidney. Diabetics should not use cysteine supplements due to its anti-insulin effects.
Cysteine and glutathione deficiency in HIV-infected patients. The basis for treatment with N-acetyl-cysteine
AIDS-FORSCHUNG (Germany), 1992, 7/4 (197-199)
Clinical studies and complementary laboratory investigations suggest that the deterioration of the immune system in HIV-infected patients may be the consequence of a virus-induced cysteine deficiency. HIV-infected persons at all stages of the disease have, on the average, decreased plasma cystine and cysteine and decreased intracellular glutathione levels. Cysteine levels also decrease in rhesus macaques within 1 to 2 weeks after infection with SIV(mac). HIV-infected persons and SIV-infected macaques also have, on the average, markedly increased plasma glutamate levels, which aggravate the cysteine deficiency by inhibiting the membrane transport of cystine. Even moderately increased extracellular glutamate levels as they are found in HIV-infected persons cause a profound decrease of intracellular cyst(e)ine levels. A correlation between individual T4+ cell counts (but not T8+ cell counts) and individual cystine and glutamate levels has been found not only in HIV-infected persons but also in healthy individuals, indicating that the linkage between cysteine supply and immune system is demonstrable even in the absence of the virus. There is suggestive evidence that the HIV-induced cysteine deficiency is not only responsible for the 'cellular dysfunction' but also for the abnormal activation which is exemplified by the lymphadenopathy syndrome and abnormal antibody production. HIV-infected persons were found to have abnormally high TNFalpha, IL-2 receptor alpha-chain and beta2-microglobulin levels. All the corresponding genes are associated with kappaB-like enhancer sequences. And the activation of the transcription factor NFkappaB is negatively regulated by cysteine or cysteine derivatives. We have, therefore, suggested that N-acetyl-cysteine (NAC) may be considered for the replenishment of cysteine and glutathione levels in HIV-infected persons, since NAC is a well-established and safe drug with well-documented pharmacokinetics.
Investigation of the protective effects of the antioxidants ascorbate, cysteine, and dapsone on the phagocyte-mediated oxidative inactivation of human alpha-1-protease inhibitor in vitro.
Am Rev Respir Dis (UNITED STATES) Nov 1985, 132 (5) p1049-54
Oxidants derived from the atmosphere or from activated pulmonary phagocytes mediate functional inactivation of alpha-1-protease inhibitor (alpha-1-PI). Chronic exposure to these oxidants may cause emphysema. In this study we have investigated the effects of the antioxidants ascorbate, cysteine (10(-4) M to 10(-1) M), and dapsone (10(-6) M to 10(-3) M) on the oxidative inactivation of human alpha-1-PI by leukoattractant-activated polymorphonuclear leukocytes (PMNL) in vitro. During exposure of alpha-1-PI to stimulated PMNL in the presence of ascorbate and cysteine at concentrations of greater than 10(-4) M and dapsone at greater than 10(-6) M, the elastase inhibitory activity of alpha-1-PI was preserved. However, exposure of the alpha-1-PI to the antioxidants subsequent to PMNL-mediated oxidative inactivation was not associated with reactivation of elastase inhibitory capacity. Ascorbate, cysteine, and dapsone at concentrations that caused 50% protection of alpha-1-PI did not affect degranulation or the binding of radiolabeled leukoattractant to PMNL. It is suggested that the protective effects of the antioxidants are related to their ability to scavenge superoxide and oxidants generated by the PMNL-myeloperoxidase/H2O2/halide system. Because the effects of ascorbate and especially those of dapsone were observed at concentrations of these agents that are attainable in vivo, our results may have clinical significance
Elevated hepatic gamma-glutamylcysteine synthetase activity and abnormal sulfate levels in liver and muscle tissue may explain abnormal cysteine and glutathione levels in SIV-infected rhesus macaques I
AIDS Research and Human Retroviruses (USA), 1996, 12/17 (1639-1641)
To establish whether the low cysteine and glutathione levels in HIV-infected patients and SIV-infected rhesus macaques may be consequences of an abnormal cysteine catabolism, we analyzed sulfate and glutathione levels in macaques. Muscle tissue (m. vastus lateralis and m. gastrocnemius) of SIV- infected macaques (n = 25) had higher sulfate and lower glutathione and glutamate levels than that of uninfected controls (n = 9). Hepatic tissue, in contrast, showed decreased sulfate and glutathione disulfide (GSSG) levels, and increased gamma-glutamylcysteine synthetase (gamma-GCS) activity. These findings suggest drainage of the cysteine pool by increased cysteine catabolism in skeletal muscle tissue, and by increased hepatic glutathione biosynthesis. Cachectic macaques also showed increased urea levels and decreased glutamine/urea ratios in the liver, which are obviously related to the abnormal urea excretion and negative nitrogen balance commonly observed in cachexia. As urea production and net glutamine synthesis in the liver are strongly influenced by proton-generating processes, the abnormal hepatic urea production may be the direct consequence of the cysteine deficiency and the decreased catabolic conversion of cysteine into sulfate and protons in the liver.
Effects of amino acids on acute alcohol intoxication in mice--concentrations of ethanol, acetaldehyde, acetate and acetone in blood and tissues.
Arukoru Kenkyuto Yakubutsu Ison (JAPAN) Oct 1990, 25 (5) p429-40
Condensation reactions between some SH-amino acids (L-and D-cysteine 1%) and acetaldehyde (50 microM) were studied in vitro experiment. In the aqueous solution, free acetaldehyde was reduced to 41.3% by L-cysteine and to 36.4% by D-cysteine. In the reaction with human blood medium, after the medium was deproteinized with perchloric acid reagent, acetaldehyde was reduced to 47.0% by L-cysteine and to 43.8% by D-cysteine. D-Cysteine appears to have great stability of reacting acetaldehyde. In vitro experiment reactability for D-cysteine exhibited 3-8% higher than that for L-cysteine. Next, effects of some amino acids on alcohol metabolism were studied in male ICR mice. The animals were given ethanol through a gastric catheter at a dose of 2 g/kg and they were intraperitoneally injected L- cysteine (300 mg/kg), D-cysteine (300 mg/kg), L-alanine (300 mg/kg) and control (saline), respectively in the period of one hour before the injection of ethanol. Blood and tissues samples were analyzed for ethanol, acetaldehyde, acetate and acetone during alcohol intoxication in mice by head space gas chromatography. In the groups administered D-cysteine and L- cysteine, the mice showed a definitely faster oxidation and disappearance of ethanol. Especially in the D-cysteine group, ethanol levels in blood, liver and brain remained lower than that in the other groups (p less than 0.01). Acetaldehyde levels in blood, liver and brain remained low by L- cysteine. Ethanol metabolites during alcohol oxidation by chemical reactabilities of L- and D-cysteine showed different distribution in the mice, respectively. In the mice received L-alanine, acetate and acetone levels in blood, liver and brain were distinctly reduced (p less than 0.01). L-Alanine is reported to supply an abundance of pyruvic acid that performs the NAD-generating system. NAD produced is introduced to alcohol metabolism and the TCA cycle. It was thus presumed that the L- or/and D- cysteine, and L-alanine was effective in acute alcohol intoxication by heavy drinking.
Protection against toxic effects of formaldehyde in vitro, and of methanol or formaldehyde in vivo, by subsequent administration of SH reagents.
Physiol Chem Phys (UNITED STATES) 1976, 8 (6) p543-50
Rapid and progressive inactivation in vitro of both alcohol dehydrogenase and aldehyde dehydrogenase by low concentrations of acetaldehyde or formaldehyde is illustrated. This inactivation can be prevented or reversed by glutathione or other SH reagents. Those effects led to investigations in vivo. Rats and mice were injected with concentrations that would result in death in approximately 10 h (methanol) and approximately 4 h (formaldehyde). When 2,3-dimercaptopropanol (BAL), cysteine, or mercaptoethanol was injected (10 min to 3 h) after administration of methanol or formaldehyde, approximately 70% of the animals survived indefinitely; the remaining 30% showed substantial increase in survival time. The findings indicate the possibility of using reagents such as BAL for human therapy and suggest that the toxicity of methanol and formaldehyde is due in part to effects other than acidosis.
Acetaminophen-induced depletion of glutathione and cysteine in the aging mouse kidney.
Biochem Pharmacol (ENGLAND) Jul 7 1992
Glutathione (GSH) plays an essential role in the detoxification of acetaminophen (APAP) and the prevention of APAP-induced toxicity in the kidney. Our previous results demonstrated that a GSH deficiency is a general property of aging tissues, including the kidney, suggesting a hypothesis that senescent organisms are at greater risk to APAP-induced renal damage. To test this, C57BL/6NIA mice of different ages through the life span were injected with various doses of APAP, and the extent of GSH and cysteine (Cys) depletion and recovery were determined. At time intervals up to 24 hr, kidney cortex samples were obtained, processed and analyzed for glutathione status, namely GSH, glutathione disulfide (GSSG), Cys and cystine, using an HPLC method with dual electrochemical detection. In the uninjected controls, GSH and Cys concentrations decreased about 30% in the aging mouse, but the GSSG and cystine levels were unchanged during the life span. APAP administration depleted the kidney GSH and Cys contents in a dose
Cysteine isopropylester protects against paracetamol-induced toxicity.
Biochem Pharmacol (ENGLAND) Feb 4 1992
Cysteine isopropylester (CIPE), a novel ester of cysteine, has been synthesized in order to evaluate its potential as a chemoprotectant. The increased lipophilicity of the ester relative to cysteine should facilitate its entry into cells where, following hydrolysis, it should act as an intracellular source of cysteine or be utilized for the synthesis of glutathione so protecting the cell against various types of chemical insult. In this study, we evaluate the ability of CIPE to protect against paracetamol-induced hepatotoxicity in mice. When administered to mice, CIPE produced a rapid but transient elevation of levels of non-protein sulphydryls (NPSH) in liver, lung, kidney and spleen. The greatest increase in NPSH was seen in the lung, but after 60 min all NPSH values had returned to control levels, demonstrating the capacity of the mouse to rapidly metabolize both CIPE and cysteine. In mice pretreated with benzo(a)pyrene, CIPE protected against paracetamol-induced toxicity as measured by the prevention of
The effect of reduced glomerular filtration rate on plasma total homocysteine concentration
Scandinavian Journal of Clinical and Laboratory Investigation (Norway), 1996, 56/1 (41-46)
The concentration of homocysteine in plasma has been shown to be increased in renal failure, possibly contributing to the accelerated atherosclerosis observed in uraemic patients. The aim of the present study was to document the relationship between plasma total homocysteine (tHcy) concentrations and glomerular filtration rates (GFR) in highly selected patients, with renal function ranging from normal to dialysis dependency. GFR was defined as the plasma clearance of iohexol; a more accurate method than the creatinine-based estimations applied in previous studies. Plasma tHcy concentrations were highly correlated to GFR (r=0.70, p<0.0001) and were significantly increased already in moderate renal failure. According to a multiple regression analysis, GFR and red cell folate concentrations independently predicted plasma tHcy concentrations, whereas those of serum creatinine, plasma pyridoxal-5-phosphate, urine albumin and urine alpha-l-microglobulin (a marker of tubular damage) did not. Thus, GFR seems to be a better determinant of plasma tHcy concentration than serum creatinine concentration. Plasma total cysteine and total cysteinylglycine concentrations followed the same pattern as those of tHcy.
Inactivation of brain and kidney aspartate aminotransferases by S-(1,2-dichlorovinyl)-L-cysteine and by S-(1,1,2,2-tetrafluoroethyl) L-cysteine
Developmental Neuroscience (Switzerland),I 1996, 18/5-6 (505-514)
Long-term exposure to trichloroethylene can cause kidney cancer in experimental animals and humans. In addition, dichloroacetylene (a breakdown product of trichloroethylene) is nephrotoxic and neurotoxic. Both trichloroethylene and dichloroacetylene are metabolized in part to the corresponding cysteine S-conjugate (i.e. S-(1,2-dichlorovinyl)-L-cysteine) which is toxic. Cysteine S-conjugate beta-lyases convert S-(1,2-dichlorovinyl)-L-cysteine to pyruvate, ammonia and a reactive fragment that adds to macromolecules, depletes cellular thiols and causes lipid peroxidation. We now show that S(1,2-dichlorovinyl)-L-cysteine and another nephrotoxic cysteine S-conjugate, S-(1,1,2,2-tetrafluoroethyl)-L-cysteine, inactivate purified cytosolic aspartate aminotransferase and purified alanine aminotransferase. These cysteine S-conjugates also inactivate aspartate aminotransferase in cytosolic and mitochondrial fractions of rat brain and kidney. The present results suggest that some halogenated xenobiotics may be toxic in part through their conversion to the corresponding cysteine S-conjugate which inactivates key pyridoxal 5'-phosphate-containing enzymes.