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)

trans-Stilbene imine (trans-1,2-diphenylaziridine) is the nitrogen analog of trans-stilbene oxide, a potent inducer of several microsomal and cytosolic xenobiotic-metabolizing enzymes. Although the acute toxicity of cis- and trans-stilbene imines prevents their application at the usual dose for trans-stilbene oxide (400 mg/kg/day), it is apparent that the imines nevertheless potently induce several xenobiotic-metabolizing enzymes in rat liver. The IP administration of trans-stilbene imine resulted in statistically significant increases in the activities of aminopyrine N-demethylase, microsomal epoxide hydrolase, glutathione transferase (toward 1-chloro-2,4-dinitrobenzene, 1,2-dichloro-4-nitrobenzene and delta 5-androstene-3,17-dione) and UDP-glucuronosyltransferase (toward testosterone). cis-Stilbene imine was less potent in inducing these activities. Although trans-stilbene imine (total dose = 400 mg/kg) was more potent than trans-stilbene oxide (total dose = 1200 mg/kg) in inducing the activities of glutathione transferase (toward 1-chloro-2,4-dinitrobenzene) and UDP-glucuronosyltransferase (toward testosterone), both compounds belong to the class of substances which are more potent inducers of conjugating (phase II) enzymes. Because of their structural similarity with K-region arene imines which are potent mutagens, cis-stilbene imine and trans-stilbene imine were investigated for mutagenicity (reversion of his- strains of Salmonella typhimurium). cis-Stilbene imine and trans-stilbene imine were direct mutagens in the strain TA100. This result, and the finding that acenaphthene 1,2-imine efficiently reverts various strains of Salmonella typhimurium, demonstrates that not only K-region arene imines, but also other aziridines substituted at the two carbons with aromatic moieties, are mutagenic.
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PMID:cis- and trans-1,2-diphenylaziridines: induction of xenobiotic-metabolizing enzymes in rat liver and mutagenicity in Salmonella typhimurium. 354 49

Guinea pig is the animal model of choice for studies on effects of ascorbic acid (AA). However, rat is one of the largely used animals for investigations related to chemical carcinogenesis. Therefore, the present study was designed to evaluate the changes induced by high intake of the vitamin in xenobiotic and carcinogen metabolizing status of the organs. Male Wistar rats, dosed daily with 50 mg AA/100 g body weight for 10 weeks, demonstrated a small non-significant increase in hepatic, pulmonary and colon cytochrome P-450 (Cyt. P-450) contents, which was accompanied with a significant increase in hepatic and pulmonary arylhydrocarbon hydroxylase (AHH) activities. Phase II enzymes of drug metabolism responded in different ways to increased intake of AA. UDP-glucuronyltransferase (UDPGT) activity was unaffected in liver and colon, but it was increased (p less than 0.005) in lung. Activities of glutathione S-transferase (GST) were decreased in the three organs. Inducibility of AHH by 3-methylcholanthrene (MCA) or phenobarbital (PB) was largely reduced due to AA feeding. Besides this, MCA and PB had differential effects on enzymatic levels in AA fed rats. When compared with our earlier observations in guinea pig, it was found that rat responded similarly to guinea pig to increased intake of AA with regard to hepatic AHH, Cyt. P-450, UDPGT and GST, pulmonary AHH, Cyt. P-450 and Cyt. b5, and all studied colon enzymes, except GST.
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PMID:Effect of excessive intake of ascorbic acid on hepatic and extra-hepatic phase I and phase II drug metabolism in rat. 356 72

Microsomal and cytosolic preparations of hepatic, renal, ileal and ruminal tissues of cattle and sheep were used to measure oxidative, hydrolative and conjugative biotransformations of 11 xenobiotic substrates. Within species, enzyme activities were generally higher (P less than .05) in hepatic than non-hepatic tissue but, in both species, non-hepatic tissue exhibited considerable capacities for metabolizing certain substrates. Sheep rumen wall (with papillae) was notably high in cytochrome P-450 content (34% of hepatic value), in glutathione conjugation of ethacrynic acid (223% of hepatic activity; P less than .05), and UDP-glucuronidation of estrone (290% of hepatic activity; P less than .05). Sheep differed (P less than .05) from cattle, having lower cytochrome P-450 content in liver and ileum (but not kidney); lower N-demethylase activity in liver, but two- to threefold higher activity in kidney; lower sulfotransferase activity in liver and kidney; and higher glutathione S-transferase activity toward certain substrates. UDP-glucuronidation varied too widely among substrates to afford strong generalization in comparisons among tissues or between species. Non-hepatic tissues in ruminants exhibit considerable capacities for oxidative, hydrolative and conjugative metabolism of xenobiotics. Sheep and cattle differ widely in hepatic and non-hepatic capacities for biotransforming certain xenobiotics.
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PMID:Characterization of xenobiotic biotransformation in hepatic, renal and gut tissues of cattle and sheep. 361 Aug 68

This study was performed in order to study the response of epoxide hydrolases in different subcellular compartments of mouse liver to treatment with various compounds. Male C57BL/6 mice were treated with 31 different compounds--including traditional inducers of xenobiotic-metabolizing systems, liver carcinogens, stilbene derivatives, endogenous compounds and various other drugs and xenobiotics. The effects on liver somatic index; protein contents in 'mitochondria', microsomes and cytosol prepared from the liver; epoxide hydrolase activity towards trans- or cis-stilbene oxide in these three fractions; microsomal cytochrome P-450 content; cytosolic and 'mitochondrial' glutathione transferase activity and cytosolic DT-diaphorase activity were then determined. Cytosolic epoxide hydrolase activity was induced by chlorinated paraffins, di(2-ethylhexyl)phthalate and clofibrate and depressed by alpha-naphthylisothiocyanate, 3-methylcholanthrene, benzil and quercitin. Radial immunodiffusion revealed similar changes in the amount of enzyme protein present, except for two cases, where the increase in amount was larger; and the enzyme seems to be inhibited by benzil. Microsomal epoxide hydrolase activity was induced by these same compounds and several others as well, including dibenzoylmethane, butylated hydroxyanisole and polychlorinated biphenyls. 'Mitochondrial' epoxide hydrolase activity towards trans-stilbene oxide was not affected by those compounds which induced the cytosolic enzyme, but increased about two-fold after treatment with 2-acetylaminofluorene, DL-ethionine, aflatoxin B1 and phenobarbital. There does not seem to be any co-regulation of different forms of epoxide hydrolase in mouse liver. In general small effects were observed on liver weight and protein contents in the different subcellular fractions. Polychlorinated biphenyls were the most potent of the 8 compounds which induced cytochrome P-450, while butylated hydroxyanisole induced cytosolic glutathione transferase activity to the highest extent. 'Mitochondrial' glutathione transferase activity was most induced by certain of the stilbene derivatives. The most potent inducers of DT-diaphorase activity were 3-methylcholanthrene, polychlorinated biphenyls and dinitrotoluene.
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PMID:Hepatic levels of cytosolic, microsomal and 'mitochondrial' epoxide hydrolases and other drug-metabolizing enzymes after treatment of mice with various xenobiotics and endogenous compounds. 362 71

The effect of exposure to malathion on several parameters of hepatic xenobiotic biotransformation was studied in male Sprague-Dawley rats. Groups of rats dosed i.p. daily for 1 or 2 weeks with 40 or 200 mg/kg malathion showed an increase in epoxide hydrolase activity (1 week, 200 mg/kg) and glutathione S-transferase activity (1 week, 200 mg/kg; 2 weeks 40 and 200 mg/kg). Aldrin epoxidation was decreased after 1 week of exposure to 200 mg/kg and by both dosage regimens after 2 weeks. After 9 weeks exposure to 40 mg/kg malathion administered i.p. 3 times per week, however, no changes in hepatic xenobiotic biotransformation were noted. The results demonstrate that only continuous exposure to high doses of malathion results in an induction of epoxide hydrolase and glutathione S-transferase activities. Inductive effects on hepatic cytochrome P-450 monooxygenase activity were not observed irrespective of whether exposure was short- or medium-term.
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PMID:Effect of length of exposure to malathion on xenobiotic biotransformation in male rat liver. 362 31

1. The effect of picloram on model xenobiotic substrate biotransformation in vivo was studied in female and male rat liver. 2. Treatment with picloram had little effect on epoxide hydratase and glutathione S-transferase activity, but caused a dose-dependent increase in ethoxyresorufin-O-deethylase activity and a concomitant decrease in aldrin epoxidase activity in male rats. 3. Treatment of male rats with equivalent doses of 2-acetylaminofluorene, 2-amino-anthracene and picloram induced ethoxyresorufin-O-deethylase activity to the same degree. 4. Treatment of female rats with picloram resulted in dose-dependent increases in ethoxyresorufin and ethoxycoumarin-O-deethylation without decreasing aldrin epoxidase activity. 5. Picloram binds to liver microsomal preparations from rats pretreated with phenobarbitone and/or 3-methylcholanthrene, giving a type I spectrum. 6. The results indicate that picloram is a 3-methylcholanthrene-type inducer, and the implications are discussed.
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PMID:Effects of picloram on xenobiotic biotransformation in rat liver. 368 62

The activity of three enzymatic systems of xenobiotic metabolism (cytochrome P-450-dependent monooxygenases, non-specific esterases and glutathione S-transferases) was studied in sensitive (S) and resistant to tetrametrin (Rtetr.), permetrin (Rperm.), mecarbenyl (Rmec.) and chlorophos (Rchlor.) strains of the housefly M. domestica L. In Rtetr. and Rmec., the activity of microsomal monooxygenases was increased 2.7- and 2.3-fold, respectively, as compared to S. The position of maxima of CO-difference spectra of cytochrome P-450 in all resistant strains (with the exception of Rchlor.) were shifted towards the short-wave region by 1-2 nm. The activity of glutathione S-transferase in Rtetr. was increased as compared to S. Analysis of the total esterase activity and electrophoresis in starch gel revealed quantitative and qualitative differences between the strains under study. In all resistant strains, except for Rmec., additional bands corresponding to the esterase activity were observed. The experimental results are discussed in terms of resistance of insects to insecticides.
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PMID:[The role of enzymes of xenobiotic metabolism in the resistance of insects to insecticides]. 369 17

Keeping male rats within a month on a ration deficient in vitamin A led to a distinct decrease in content of cytochrome P-450, in activities of carboxylase, epoxide hydrolase, aniline hydrolase and to a slight inhibition of UDP-glucuronosyl transferase in live tissue. At the same time, activity of glutathione transferase and content of reduced glutathione in liver tissue were increased. After administration of the epoxide-containing T-2 mycotoxin into rats within 10 days at a dose of 0.54 mg/kg activity of the enzymes catalyzing metabolism of xenobiotics was inhibited in the animals maintained on the complete half-synthetic ration, except of epoxide hydrolase and glutathione transferase, activity of which was elevated. The administration of T-2 toxin under conditions of deficiency in vitamin A caused especially distinct inhibition of the enzymes involved in the 1 phase of xenobiotic metabolism but it was accompanied by only slight increase in T-2 toxicosis. The enzymes participating in conjugation of xenobiotics as well as epoxide hydrolase appear to play major roles in detoxication of T-2 mycotoxin.
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PMID:[Activity of enzymes of xenobiotic metabolism in the liver of rats with vitamin A deficiency and mycotoxicosis T-2]. 370 7

Toxic effects of SO2 and sulfite such as bronchitis and bronchoconstriction have been well documented. SO2 has also been suggested to potentiate carcinogenic effects of PAH. However, the molecular basis of these toxic effects is unclear. We have examined the covalent reaction of SO2 and sulfite with cellular proteinacious and nonproteinaceous sulfhydryl compounds using rat liver, and lung and human lung derived A549 cells. Reactions of sulfite and protein in rat and human lung cells reveals at least three proteins with sulfite-reactive disulfide bonds. Besides fibronectin and serum albumin, which had been reported to contain sulfonated products following exposure to sulfite, we have found one other protein with sulfite-binding capabilities. Since the integrity of disulfide bonds is crucial to the tertiary structure and thus protein function, the disruption of protein structure by sulfitolysis may result in altered cellular activities leading to biochemical lesions. Using carefully controlled conditions, reproducible GSH contents can be found in cultured cells and used as an experimental basis for studying alterations in the GSH and GSSG content of cells. Sulfitolysis of GSSG results in the formation of GSSO3H in A549 cells, and possibly in the lung. GSSO3H can be reduced enzymatically by GSSG reductase. However, the Km of GSSO3H is high compared to that of GSSG, suggesting the existence of a transient concentration of GSSO3H once it is formed. Cysteine S-sulfonate is, however, not reduced by cytosolic extracts in the presence of NADPH and would have to be eliminated from the cell by other means. GSSO3H is a strong competitive inhibitor of GST in rat liver and lung and A549 cells, using 1-chloro-2,4-dinitrobenzene as a substrate. It also inhibits the formation of GSH conjugates of BP 4,5-oxide, anti and syn BPDE, but to a lesser extent. These results suggest that SO2 may affect the detoxification of xenobiotic compounds by inhibiting, via formation of GSSO3H, the enzymatic conjugation of GSH and reactive electrophiles. Since GSH conjugation represents the major pathway of elimination of BP epoxides in the lung, our results offer a possible explanation for the cocarcinogenicity of SO2 with PAHs. These data suggest that the sulfitolysis reaction of sulfite is the common reaction mechanism mediating the underlying biochemical reactions leading to both the toxic and cocarcinogenic properties of SO2. Quantitation of sulfitolysis products and their interaction with cellular processes should provide a coherent scheme relating SO2 and sulfite toxicity among animal species and humans.
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PMID:Covalent reactions in the toxicity of SO2 and sulfite. 376 76

The influence of dietary R-goitrin on components of the xenobiotic-metabolizing system was examined in the liver and small intestine of male Sprague-Dawley rats. Given at a level of 200 ppm in the diet for 14 days, the R-goitrin caused a statistically significant (P less than 0.05) 21% increase in liver weight relative to body weight. A less pronounced, but statistically significant, 11% increase in relative liver weight resulted from the administration of R-goitrin at 40 ppm in the diet. Hepatic glutathione S-transferase (GST) activity was significantly increased 1.5- and 2-fold over the basal level at concentrations of 40 and 200 ppm R-goitrin, respectively. Hepatic microsomal epoxide hydratase (EH) activity was also significantly increased. Hepatic EH activity was 1.6- and 3.3-fold greater in the 40- and 200-ppm R-goitrin groups, respectively, than in the control group given the basal diet. R-Goitrin at 200 ppm in the diet produced significant 1.2- and 1.4-fold increases of GST and microsomal EH activities, respectively, in the mucosa of the small intestine. The administration of R-goitrin at 40 or 200 ppm in the diet had no significant effect on either hepatic or intestinal ethoxycoumarin O-deethylase activity.
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PMID:Effects of dietary R-goitrin on hepatic and intestinal glutathione S-transferase, microsomal epoxide hydratase and ethoxycoumarin O-deethylase activities in the rat. 387 68


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