Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of ethanol on the initiation of diethylnitrosamine- (DEN) induced liver carcinogenesis was investigated in rats. In the first experiment, eight-week-old male Wistar rats were maintained on four liquid diets: a basal diet (Group 1), a low-carbohydrate (low-CHO) diet (Group 2), a basal diet+ethanol (Group 3), or a low-CHO diet+ethanol (Group 4). After three weeks on these diets, 50 mg/kg of DEN was injected intraperitoneally. The plasma glutamic-oxaloacetic transaminase activity in Group 4 was higher 24 hours after DEN administration than in Groups 1 and 3. The plasma glutamic-pyruvic transaminase activity in Groups 3 and 4 was higher than in Groups 1 and 2. The number of gamma-glutamyltranspeptidase-positive foci per unit liver area 41 weeks after DEN administration was higher in Group 4 than in Group 1. The area of gamma-glutamyltranspeptidase-positive foci was greater in Groups 2 and 4 than in Group 1. In the second experiment, Groups 1 and 4 were given DEN orally (25 or 75 mg/kg). Plasma glutamic-oxaloacetic transaminase and glutamic-pyruvic transaminase activities 24 hours after DEN administration were significantly higher in Group 4 than in Group 1, but only when the dose of DEN was 75 mg/kg. In contrast, the number and area of placental glutathione S-transferase-positive foci per unit liver area were greater in Group 4 than in Group 1 only after 25 mg/kg of DEN. Thus the severity of hepatotoxicity and the incidence of precancerous liver lesions were not necessarily correlated. These findings together indicate that a combination of ethanol and a low-CHO diet enhances DEN-induced liver carcinogenesis in rats by increasing the bioactivation of DEN in the liver.
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PMID:Ethanol ingestion combined with lowered carbohydrate intake enhances the initiation of diethylnitrosamine liver carcinogenesis in rats. 135 84

The effect of bucillamine (BA) on glutathione (GSH) and GSH-related enzymes was investigated in C57 mouse. Administration of high doses of BA (150-400 mg/kg) produced a dose-dependent depletion (20-44%) of hepatic GSH, which was similar in magnitude to that produced by equimolar doses of other sulphydryl drugs studied previously. GSH depletion after acute BA administration correlated well with the elevation of serum glutamic-pyruvic transaminase (SGPT) (6-9-fold increase above control). The increase in SGPT after chronic administration (7 days), although significantly higher than the controls, was however much less than after acute administration. The hepatic GSH concentrations of mice given 7 days of BA were similar to the controls, again correlating well with SGPT activity. Administration of BA (150-400 mg/kg) caused also a significant dose-dependent increase in the oxidized glutathione (GSSG) in blood by 2-7-fold, as well as a dose-dependent increase in blood glutathione S-transferase (GST) activity (2-13-fold). In an in vitro experiment, hepatic GST activity was activated by various concentrations of BA (1 microM-1mM). There was little or no effect on GSSG reductase and on glutathione peroxidase (GSH-Px) after acute administration of BA. Chronic administration of BA had no effect on hepatic GSSG reductase and GSH-Px, but GSSG reductase activity in blood was increased significantly by 4-fold. It is possible that BA may affect the redox status through auto-oxidation and oxidation with endogenous thiols such as glutathione, affecting GSH concentrations and the GSH/GSSG ratio in tissues and, thus, having both metabolic and toxicological consequences. Whether or not the induction of GST activity in vivo in blood and in vitro in liver enzyme preparations shared the same underlying mechanism(s) requires further investigation.
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PMID:The effects of bucillamine on glutathione and glutathione-related enzymes in the mouse. 186 40

The effect of carbon tetrachloride (CCl4) treatment on plasma and liver cytosolic glutathione S-transferase (GST) activities was investigated in rats. CCl4 was intraperitoneally administered at a dose of 0.5 ml/kg. The elevation of plasma GST activity paralleled the increase of plasma glutamate pyruvate transaminase activity after the administration of CCl4. Liver cytosolic GST activities were significantly decreased by CCl4 treatment. To establish the relationship of plasma GST with liver cytosolic isozymes, Western blot analysis using antibodies against cytosolic GST 1-2 and 3-4 was performed. The Western blots showed the existence of GST 1-2 and 3-4 in plasma at 24 hr after CCl4 treatment. The data thus strongly suggest that cytosolic GSTs are lost from the liver to plasma as a consequence of liver damage. The Western blot analysis of plasma GST may be useful for monitoring liver damage.
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PMID:Plasma glutathione S-transferase in carbon tetrachloride treated rats and its association to hepatic cytosolic isozymes. 337 33

Male Sprague-Dawley rats received an intraperitoneal injection of 0.25-, 0.5-, 1.0-, 2.5-, and 5.0-mmol/kg dose of bromobenzene in corn oil. The metabolic fate of bromobenzene was studied by measuring its various urinary metabolites 24 h following bromobenzene administration. The hepatotoxicity of bromobenzene was estimated by determination of the serum glutamic-oxaloacetic and glutamic-pyruvic transaminase activities (SGOT and SGPT) 24 h after dosing. Treatment of rats with bromobenzene at up to 0.5 mmol/kg did not influence the transaminase activities, but significant increases in such activities began to manifest at a dose of 1 mmol/kg. However, no further increase in hepatotoxic response was induced on exposure to higher doses (2.5 and 5.0 mmol/kg) of bromobenzene. The urinary excretion of toxic doses of bromobenzene was nonlinear, based on the quantitative composition of various urinary metabolites. Furthermore, the fraction of the dose converted to thioethers, p-bromophenol, m-bromophenol, and total phenolic metabolites decreased with increasing toxic dose, suggesting their formation to be capacity-limited. The ratios of thioethers to total phenolic metabolites, of thioethers to p-bromophenol, and of thioethers to o-bromophenol decreased with increasing dose of bromobenzene. The correlation of the dose-dependent fate of metabolic excretion of bromobenzene with the results of the dose-hepatotoxic response curves supports the conclusion that there exists an apparent threshold dose (approximately 1-2.5 mmol/kg) for the toxic effects of bromobenzene that coincides with saturation of the metabolic pathways involving both glutathione/glutathione S-transferase(s) and formation of certain phenolic derivatives for its detoxification. All these results further suggest a role of a saturable, metabolic activation process involving 3,4-epoxide rather than 2,3-epoxide of bromobenzene in the development of its hepatotoxicity.
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PMID:Dose-dependent metabolic excretion of bromobenzene and its possible relationship to hepatotoxicity in rats. 650 40

The in vivo effects of human placental extract (1-4 ml/kg) on hepatic lipid peroxidation, blood and liver glutathione (GSH) levels and several enzymes associated with the antioxidant defence mechanism; i.e., catalase, glutathione peroxidase, glutathione reductase and glutathione S-transferase, together with some blood biochemical responses were investigated in rats. At an optimal dose level (4 ml/kg), a single acute intraperitoneal administration of the extract caused a significant enhancement (49.9%; p < 0.001) of lipid peroxidation with a decline in GSH level both in blood (45.1%; p < 0.001) and liver (61.0%; p < 0.001) in comparison to control animals. Activities of catalase, glutathione peroxidase and glutathione reductase were inhibited in a dose-responsive way by the treatment with the extract which also increased the activity of glutathione S-transferase in a dose-dependent manner. The extract was found to be hepatotoxic in terms of elevation of serum glutamate oxaloacetate transaminase, serum glutamate pyruvate transaminase, serum lactate dehydrogenase and blood methemoglobin concentration. Results of this study suggest the adverse consequences of the administration of the extract due to its substantial ability to alter normal cellular processes.
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PMID:Elevated lipid peroxidation, decreased glutathione levels and changes in glutathione-related enzymes in rats treated with human placental extract. 821 15

Cadmium induced lipid peroxidation (LPO) and the activity of antioxidant enzymes after the administration of a single dose of CdCl2 (0.4 mg kg-1 body wt, i.p.) was studied in rat erythrocytes. Cd intoxication increased erythrocyte LPO along with a decrease in superoxide dismutase (SOD) up to three days of Cd treatment. The decrease in erythrocyte catalase (CAT) activity was marked within 9 h of Cd intoxication. After three days of Cd treatment, LPO decreased towards normal, along with an increase in erythrocyte SOC and CAT activity. Blood glutathione (GSH) decreased significantly within 24 h of Cd treatment, followed by an increase towards normal. Erythrocyte glutathione S-transferase (GST) activity increased up to 10 days of Cd intoxication, probably in an attempt to reduce Cd toxicity. Serum glutamate pyruvate transaminase (SGPT), serum alkaline phosphatase (SALP) and serum bilirubin increased up to 10 days of Cd intoxication. Blood urea increased significantly up to three days, followed by a decrease towards normal. The results show that Cd induced LPO was associated with a decrease in antioxidant enzymes and GSH in erythrocytes; as these antioxidants increase in erythrocytes with recovery from Cd intoxication, the Cd induced LPO reversed towards normal. The increase in the SGPT, SALP and serum bilirubin correlated with LPO. The results suggest that Cd intoxication induces oxidative stress and alters the antioxidant system, resulting in oxidative damage to rat erythrocytes.
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PMID:Lipid peroxidative damage on cadmium exposure and alterations in antioxidant system in rat erythrocytes: a study with relation to time. 954 68

A rare outbreak of acute hepatic damage in workers exposed to dichloropropanols (DCPs) was reported recently. The purpose of the present study is to examine the effects of DCPs on various organs, the dose dependency and the pathogenetic potential of DCP hepatotoxicity. A single intraperitoneal injection was given to six groups of rats with 0.2 ml of 20% ethanol (control), or 1/8 x, 1/4 x, 1/2 x, 1 x, and 2 x LD50 (0.11 ml/kg) of 1,3-dichloro, 2-propanol (DC2P) diluted in 20% ethanol. After blood samplings, all organs were subjected to histologic examinations with light and electron microscopes. Fresh liver tissues from further 4 control and 4 experimental rats sacrificed 6 hours after the injection of 20% ethanol and 1 x LD50 of DC2P were homogenized and subjected to evaluate lipid peroxidation, glutathione S-transferase activity and reduced glutathione contents in the liver. The rats administered with only ethanol or 1/8 and 1/4 LD50 of DC2P showed no serological or histopathological abnormalities. Marked elevation of serum glutamate pyruvate transaminase (SGPT) with a diffuse massive necrosis of the liver cells were noted in all rats of both the 1 x and 2 x LD50 groups, and irregular zonal necroses were found in 3 of 4 rats injected with 1/2 LD50. There were no serious toxic changes in other organs. Hepatic malondialdehyde level was significantly increased, associated with decreases of liver glutathione S-transferase activity and reduced glutathione content. It was concluded that the serious DC2P-toxicity was mainly found in the livers, dose dependently, and one of the causative mechanisms of this hepatotoxicity might be the lipid peroxidation.
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PMID:Dose-dependent effects of dichloropropanol on liver histology and lipid peroxidation in rats. 981 Jan 44

There are few reports regarding the effects of benzene and ethanol being administered simultaneously. In our experiments with 4 groups (controls, ethanol, benzene and ethanol plus benzene) Wistar male rats were treated with ethanol (20%) for 5 weeks, and then exposed to benzene (0.26 g/kg) for 5 days per week for 3 weeks. We also investigated the effects of benzene on the body weight, organ weight, peripheral hematology and hepatic drug metabolizing enzymes in the ethanol administrated rats. The liver weight increased significantly, but spleen weight decreased significantly in the benzene exposed group. Hematological examination showed a decrease of leukocyte in the two groups of benzene and ethanol plus benzene in comparison with the controls, but an effect promoted by ethanol was not found. Serum glutamate oxaloacetate transaminase (SGOT) and serum glutamate pyruvate transaminase (SGPT) values were not significantly different in the exposure groups when compared with the controls. The contents of microsomal cytochrome P450 in all the exposed groups showed a tendency to increase, but they were not significantly different in comparison with the controls. On the other hand, hepatic glutathione S-transferase activity in the exposed groups increased significantly.
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PMID:[Effect of benzene exposure on hematology and hepatic drug metabolic enzymes in ethanol administrated rats]. 1020 90

Extracts of Emblica officinalis (EO), Phyllanthus amarus (P. amarus) and Picrorrhiza kurroa (P. kurroa) significantly inhibited hepatocarcinogenesis induced by N-nitrosodiethylamine (NDEA) in a dose dependent manner. The anticarcinogenic activity of these extracts were evaluated by their effect on tumour incidence, levels of carcinogen metabolizing enzymes, levels of liver cancer markers and liver injury markers. Animals treated with NDEA alone showed 100% tumour incidence and significantly elevated tissue levels of drug metabolizing enzymes such as glutathione S-transferase (GST) and aniline hydroxylase (AH). Treatment of extracts significantly reduced these levels. Levels of gamma-glutamyl transpeptidase (GGT) were also found to be elevated both in serum and tissues of tumour bearing animals, while they were significantly reduced in the treated group. Similar reduction was seen in tissue levels of reduced glutathione. Serum levels of lipid peroxide (LPO), alkaline phosphatase (ALP) and glutamate pyruvate transaminase (OPT), which are markers of liver injury, were also elevated. Morphology of liver tissue and levels of marker enzymes indicated that these extracts offered protection against chemical carcinogenesis.
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PMID:Effect of Emblica officinalis, Phyllanthus amarus and Picrorrhiza kurroa on N-nitrosodiethylamine induced hepatocarcinogenesis. 1021 33

Transient sublethal hyperthermia and the recovery from this exposure to heat (heat shock preconditioning) provides a cytoprotective effect on oxidative insults through an intracellular protective response, heat shock response. The impact of heat shock preconditioning on hepatic microvascular failure, which is a causative determinant of ischemia/reperfusion-induced injury of the liver, was investigated by using intravital fluorescence microscopy. In Sprague-Dawley rats, normothermic ischemia was induced by totally clamping the hepatoduodenal ligament for 20 min, followed by 120 min of reperfusion. Heat shock preconditioning was performed by whole-body hyperthermia (42 degrees C for 15 min) and subsequent 48 h recovery. In accordance with the prominent induction of heat shock protein 70 in the liver tissue, the postischemic decrease in sinusoidal perfusion rate and sinusoidal diameter, and the postischemic increase in the number of stagnant leukocytes in sinusoids and adherent leukocytes in postsinusoidal venules were significantly attenuated in the heat shock-treated animals. Furthermore, liver enzyme release (glutamate pyruvate transaminase and alpha-glutathione S-transferase) was significantly reduced and postischemic deterioration of bile production was attenuated. The 7-day survival rate after 20-minute ischemia was significantly improved from 50% to 80% (heat shock-nontreated group vs. heat shock-treated group, P < 0.05). These results indicate that heat shock preconditioning attenuates ischemia/reperfusion-induced hepatic injury by preventing postischemic microvascular disturbances, and that its protective effect is circumstantially associated with the concomitant induction of heat shock protein 70.
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PMID:Reduction of hepatic microcirculatory failure caused by normothermic ischemia/reperfusion-induced injury by means of heat shock preconditioning. 1056 6


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