Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D00031 (Glutathione)
 5,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Sulfation activity towards N-hydroxy-2-acetylaminofluorene and 4-nitrophenol was determined in male rat liver cytosol at several time points after partial hepatectomy corresponding to G1-, S-, and M-phase. N-hydroxy-2-acetylaminofluorene sulfation activity decreased by 80% when hepatocytes entered the G1-phase. This lower activity was maintained during the S-phase and M-phase, but was restored when hepatocytes entered the G0-phase again. Sulfation activity towards 4-nitrophenol did not alter after hepatectomy. Various other cytosolic enzyme activities were determined after hepatectomy to investigate the specificity of the decrease in sulfation activity. Lactate dehydrogenase and glucose-6-phosphate dehydrogenase activities were increased in the S- and M-phase by maximally 80% and 60%, respectively. Glutathione-S-transferase and glutamate-pyruvate transaminase activity did not alter during the cell cycle. These results indicate that sulfation of N-hydroxy-2-acetylaminofluorene in hepatocytes may depend on the phase of the cell cycle. The relevance of the finding is discussed in relation to the resistance of proliferating (pre)neoplastic hepatocytes to the toxic and mitoinhibitory effects of N-hydroxy-2-acetylaminofluorene.
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PMID:Bioactivation of the hepatocarcinogen N-hydroxy-2-acetylaminofluorene by sulfation in the rat liver changes during the cell cycle. 140 47

Drugs and chemicals that cause irreversible damage to cells may do so by producing specific defects in calcium regulation. The present studies examined glycogen phosphorylase as an index for assessing in vivo changes leading to excessive calcium ion activity, a putative pathogen, during the course of acetaminophen-induced liver injury. Administration of 500 mg/kg acetaminophen per os to mice depleted hepatic glutathione to a nadir by 1 h. Covalent binding to hepatocellular macromolecules commenced at this time and then rose out of the non-injurious background range at 1.5 h, coincident with a sharp rise in phosphorylase a activity. Phosphorylase activation preceded the leakage of alanine aminotransferase into plasma by several hours but appeared only after glutathione was depleted in excess of 80%. During the first 3 h, phosphorylase a activity rose in direct proportion to the amount of acetaminophen covalent binding. Glutathione depletion alone was not responsible for phosphorylase activation because the glutathione biosynthesis inhibitor, D,L-buthionine sulfoximine, produced comparable glutathione depletion but failed to stimulate phosphorylase activity or produce cell injury. Because phosphorylase a activity is thought to mirror changes in Ca2+ activity in vivo, these results support the hypothesis that acetaminophen-induced hepatocellular injury is related to the impairment of Ca2+ regulation.
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PMID:Immediate rise in intracellular calcium and glycogen phosphorylase a activities upon acetaminophen covalent binding leading to hepatotoxicity in mice. 338 36

Ethanol at initial concentrations between 0.75 and 6 g/l produced a dose-dependent release of the enzymes glutamic-pyruvic-transaminase and sorbitol dehydrogenase (GPT, SDH) from the isolated perfused rat liver. At the concentration of 6 g/l, it also decreased the oxygen consumption and elevated the calcium content of the isolated livers. These toxic effects of ethanol were significantly enhanced in livers, the glutathione content of which had been depleted by pretreatment with phorone. Ethanol-induced toxicity in glutathione-depleted isolated livers could be prevented both by inhibition of alcohol dehydrogenase with 4-methylpyrazole and of xanthine oxidase with allopurinol. In rats, in vivo, 1.6 g/kg ethanol injected intravenously produced a small increase in serum GPT and SDH concentrations 4 h after its administration. This increase in enzyme activities was several-fold higher and longer lasting in rats pretreated with phorone. Glutathione depletion per se did not induce hepatotoxicity in vitro or in vivo. Since glutathione is involved in several lines of defense against oxidative damage, our results of an enhanced susceptibility of glutathione-depleted livers to ethanol toxicity favour the hypothesis that ethanol exerts its hepatotoxic action via an activation of molecular oxygen.
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PMID:Enhancement by glutathione depletion of ethanol-induced acute hepatotoxicity in vitro and in vivo. 360 86

Treatment of rats with nifurtimox, a nitrofuran derivative widely used for the treatment of Chagas' disease, induced a time- and dose-dependent depletion of liver glutathione, maximal effects being obtained with 200 mg nifurtimox/kg body weight. Extra release of both oxidized (GSSG) and reduced (GSH) glutathione into bile contributed to this depletion. Glutathione excretion into bile accounted for only part of liver glutathione loss, thus indicating that, in addition to the GSH-peroxidase reaction (resulting in GSSG generation), other glutathione-related processes were involved in nifurtimox detoxification. Bile flow, bile salt excretion, liver lipid conjugated diene content, liver glutathione reductase and glutathione peroxidase activities, and serum alanine aminotransferase (ALAT) activity were not affected by the nifurtimox treatment, thus ruling out widespread damage of the liver cell by nifurtimox. Nevertheless, the extra GSH release in the nifurtimox-treated rats may indicate an alteration of the hepatocyte membrane.
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PMID:Increased biliary secretion and loss of hepatic glutathione in rat liver after nifurtimox treatment. 684 98

Studies have shown that ethanol at moderate concentrations inhibits epidermal growth factor-dependent replication of fetal rat hepatocytes in culture. This may account for the growth/development impairment associated with fetal alcohol syndrome and decreased liver regeneration in alcoholic liver disease. In this study, we further define the mechanism(s) of the negative impact of ethanol on fetal rat hepatocytes and provide evidence that ethanol-induced injury to these cells is associated with membrane damage caused by lipid peroxidation, altered cell glutathione homeostasis and deranged mitochondrial structure and function. Exposure of fetal rat hepatocyte replication to ethanol (2 mg/ml) promptly resulted in blockade of replication, as indicated by a 40% reduction in DNA synthesis (p < 0.05). Assessment of cell injury on the basis of lactate dehydrogenase and ALT leakage indicated a statistically significant but not appreciable effect, whereas 51Cr leakage was more substantially increased (p < 0.05). Within 6 hr of ethanol exposure, superoxide radical levels increased more than twofold (p < 0.05). We noted a 56% increase in levels of diene conjugates, a 131% increase in malonaldehyde concentration and a 66% increase in fluorescent products of lipid peroxidation (all p < 0.05). Glutathione levels were decreased to 47% below control values (p < 0.05). Electron microscopic studies illustrated a slight disruption of mitochondrial structure (enlargement of mitochondria and dilation of cristae). This disruption was accompanied by mitochondrial swelling (increased permeability), altered mitochondrial membrane potential (a 16% decrease in rhodamine uptake), a 28% decrease in succinate dehydrogenase activity and a 30% decrease in cellular ATP level (p < 0.05). Pretreatment of fetal rat hepatocytes with 0.1 mmol/L N-acetylcysteine or S-adenosylmethionine for 24 hr prevented the ethanol-induced reduction of ATP and glutathione levels, essentially restored cell replication, ameliorated 51Cr leakage and decreased malonaldehyde and diene conjugate levels to 41% to 65% and 25% above control values, respectively. Pretreatment with 0.1 mmol/L vitamin E fully normalized malonaldehyde and diene conjugate levels and 51Cr leakage but failed to improve ATP levels or to increase significantly cell replication and glutathione levels. Concomitant administration of glutathione precursors with ethanol, rather than pretreatment, did not alter the impaired cell replication. Thus our data underscore the importance of cellular glutathione and ATP in preventing ethanol-induced decreases in fetal cell replication and suggest that alleviation of cellular lipid peroxidation alone is not sufficient to prevent this abnormality in fetal rat hepatocyte function.
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PMID:Effect of ethanol on rat fetal hepatocytes: studies on cell replication, lipid peroxidation and glutathione. 835 6

Groups of female Fischer-344 rats were fed a semipurified choline-deficient (CD) diet, or a semisynthetic L-amino acid-defined choline-deficient (CDAA) diet, for up to 12 wk and effects of the 2 diets on the liver were compared. Steatosis was diffuse and more severe throughout in rats fed the CDAA diet than in rats fed the CD diet. Greater elevations in serum aspartate and alanine aminotransferase activities were also present in the former rats, along with higher 2-bromodeoxyuridine labeling indices in the liver. Discrete amounts of 8-hydroxyguanine were detected in liver DNA, but were not significantly different in rats fed the 2 diets, or from those present in a group of control rats killed at 0 time. Glutathione S- transferase placental form-positive focal lesions were not observed in any of the rats. The results show that the CDAA diet causes more severe degrees of steatosis and liver cell death and proliferation than the CD diet, raising the possibility that it may, in contrast to the CD diet, result in the eventual induction of hepatocellular carcinomas in female Fischer-344 rats.
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PMID:Comparative changes in the liver of female Fischer-344 rats after short-term feeding of a semipurified or a semisynthetic L-amino acid-defined choline-deficient diet. 857 1

Hepatoprotective effect of Tamra bhasma has been studied on cumene hydroperoxide (CHP) induced peroxidation, reduced glutathione content and superoxide dismutase (SOD)-in rat liver homogenate. The drug was orally given for 8 days which showed significant reduction in the level of malondialdehyde (MDA) production at different concentrations of cumene hydroperoxide in vitro. Glutathione content was maintained upto seventy minutes and SOD activity was enhanced to 166%. These animals did not show any rise in serum GOT and GPT. On similar doses no histological changes were observed in liver. The results suggested that Tamra bhasma is a strong antioxidant drug and could be used in the management of lipid peroxidation with no detectable adverse effect.
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PMID:Role of Tamra bhasma, an Ayurvedic preparation, in the management of lipid peroxidation in liver of albino rats. 869 11

Glutathione (GSH) is the major intracellular antioxidant and is essential to normal cell function and replication. Cysteine and other thiol compounds have been considered rate-limiting for GSH biosynthesis, but recent studies have demonstrated that glutamine (GLN) becomes essential during metabolic stress to replete tissue GSH levels which have become depleted. To determine the role of GLN supplementation in the resting, nonstressed state, we studied three groups of Wistar rats. The animals were catheterized and randomly assigned to one of three groups; (1) chow ad libitum group receiving iv saline (control), (2) standard total parenteral nutrition (STA-TPN) group, and (3) glutamine-enriched TPN (GLN-TPN) group. The intravenously fed animals received no rat chow. The infusions were administered at a rate of 2.2 ml/hr for 4 days and all animals were harvested on the fifth day of study. The GLN-TPN group had a significantly higher plasma GSH level than STA-TPN or control animals (P < 0.01). The hepatic concentration of GSH and the oxidized GSH/reduced GSH were similar in all groups. GLN-TPN had a significantly lower plasma ALT level than the control group (P < 0.05). The control group had a significantly higher ALP level than STA-TPN and GLN-TPN animals (P < 0.01). There were no significant differences in other measures of hepatic functions among the three groups. Our data demonstrate that in this model GLN-enriched TPN enhances plasma GSH concentrations, while maintaining hepatic GSH stores. This suggests that GSH turnover is altered during glutamine-enriched TPN, which may explain how dietary GLN supplementation enhances tissue antioxidant capacity.
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PMID:Glutamine-enriched total parenteral nutrition enhances plasma glutathione in the resting state. 876 39

Hepatoprotective effect of Hepatomed (an ayurvedic drug containing water extract of 6 medicinal plants) has been studied on cumene hydroperoxide (CHP) induced lipid peroxidation and reduced glutathione content in rat liver homogenate. In vitro experiments show significant reduction in the level of malondialdehyde (MDA) induced by 1.5 mM cumene hydroperoxide(CHP). Glutathione content was almost maintained to normal in drug treated rats. Oral treatment of drug up to 3 ml/100 g body weight for 15 days did not show any rise in serum GOT and GPT. On similar doses, significant choleratic effect was observed without any adverse histological changes after 4 days treatment. The results suggest that 'Hepatomed' is a strong hepatoprotective ayurvedic medicine with no detectable adverse effects.
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PMID:Hepatoprotective and toxicological evaluation of hepatomed, an ayurvedic drug. 913 72

The effects of black tea (Camellia sinensis L.) on lipid peroxidation and glutathione (GSH) levels in carbon tetrachloride (CCl4)-treated female Wistar rats were examined. Two control groups and one treatment group were tested. The control groups were fed with a standard diet, while the black tea group was fed the standard diet plus 6% by weight dried black tea leaves. At the end of 2 months, a single dose of CCl4 (1 ml/kg, i.p.) in olive oil was administered to rats in one of the control groups and the black tea group. They were sacrificed after 2 hours. Rats in the other control group were administered olive oil in a similar fashion. Measurements were made of lipid peroxide levels in liver and plasma, glutathione levels in liver, and alanine transaminase (ALT) and aspartate transaminase (AST) activities in plasma. Liver lipid peroxide levels, plasma ALT and AST activities were significantly decreased in the black tea group compared with the CCl4-treated control group, while plasma lipid peroxide levels were not. These results are parallel to those previously found with Wistar male rats. Glutathione levels, however, were not significantly affected, in contrast to the data relating to male rats, either after CCl4 or black tea treatments. The results of our study add to the findings that black tea attenuates CCl4-induced hepatic injury but also indicates the susceptibility of glutathione levels to endocrinological effects.
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PMID:Effect of black tea on lipid peroxide and glutathione levels in female rats. 1120 8


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