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)

Polybrominated biphenyls (PBBs) are structurally very close to polychlorinated biphenyls (PCBs) which are known to be potent inducers of xenobiotic biotransformation reactions. We have studied the effects of 2 industrial PBB-mixtures, "hexabromobiphenyl" (HBB) and "octabromobiphenyl" (OBB), on enzymes catalyzing drug hydroxylation, epoxide hydration, and conjugation reactions in different tissues of C57 mice. The enzyme activities were measured 10 days after a single i.p. injection of PBBs (75 mg/kg). HBB enhanced the activities of hepatic AHH (1.9-fold), ethoxycoumarin deethylase (5.7-fold), epoxide hydratase (1.5-fold), glutathione S-transferase (1.7-fold) and UDP-glucuronosyltransferase (1.5-fold). In the kidney HBB enhanced the activity of UDP-blucuronosyltransferase 1.5-fold. OBB caused in increase in the activities of liver AHH (1.5-fold), ethoxycoumarin deethylase (2.4-fold) and glutathione S-transferase (1.4-fold). A slight increase was also seen in the activity of UDP-glucuronosyltransferase in digitoninactivated liver microsomes of OBB-treated mice. In the kidney OBB caused a slight but statistically significant decrease in glutathione S-transferase activity. Intraperitoneally injected bromobiphenyls had no effects on these drug metabolizing enzymes in the lung of C57 mice. These results were similar to the effects caused by a mixture of PCBs.
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PMID:Effect of polybrominated biphenyls on drug metabolizing enzymes in different tissues of C57 mice. 21 61

Inhalation of cigarette smoke specifically induces the rat lung and kidney aryl hydrocarbon hydroxylase (AHH) in less than 4 h. The epoxide hydratase (EH) and the glutathione S-transferase are not significantly modified by a similar treatment in any of the rat tissues. Compared to the kidney AHH, the lung hydroxylase is 3--4 times more sensitive to small concentrations of cigarette smoke and seems to have a longer biological half-life. In both tissues, the induced AHH presents the same in vitro sensitivity to various inhibitors as a polycyclic hydrocarbon induced AHH. In primary fetal rat liver cell culture, the cigarette smoke condensate fractions (CSCF) induce both the AHH and EH activity. Nevertheless, the AHH activity responds faster and to lower concentrations of CSCF than the EH activity. The liver cell culture constitutes a unique tool for a comparative study of the AHH and EH induction mechanism. Low concentration (10 muM) of benz(a)anthracene induces only the AHH activity while trans-stilbene oxide enhances selectively the EH activity. Appropriate concentrations of CSCF or of phenobarbital (PB) determine a parallel induction of both enzymes. The results are discussed on the basis of (a) the existence of specific mechanisms of AHH regulation in the lung and in the kidney and (b) the existence of coordinated or independent biochemical control of the AHH and EH activity.
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PMID:Organ specificity of induction of activating and inactivating enzymes by cigarette smoke and cigarette smoke condensate. 28 33

Methadone . HCl given in the drinking water for 4 weeks increased microsomal epoxide hydratase activity in the liver of adult male Wistar rats, with no change in aryl hydrocarbon hydroxylase activity. In contrast, in female rats it raised aryl hydrocarbon hydroxylase with no change in epoxide hydratase activity. Gonadectomy altered the effect of methadone on epoxide hydratase, but not on aryl hydrocarbon hydroxylase activity, in both sexes. In ovariectomized rats, but not in controls, methadone nearly doubled the epoxide hydratase activity, whereas in male rats castration decreased the inductive effect of methadone. Gonadectomy had a significant effect on the results of methadone treatment with respect to glutathione S-transferase activity in female rats. A sex difference was noted in the control levels of aryl hydrocarbon hydroxylase and glutathione S-transferase, but not of epoxide hydratase activity. The glutathione S-transferase and aryl hydrocarbon hydroxylase activities were decreased in castrated male rats, whereas epoxide hydratase activity was unaltered. It is concluded that sex hormones play an important role in the induction of epoxide hydratase and glutathione S-transferase by methadone, but not of aryl hydrocarbon hydroxylase, at this particular dosage regime.
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PMID:The effects of gonadectomy on the hepatic activities of aryl hydrocarbon hydroxylase, epoxide hydratase, and glutathione S-transferase in Wistar rats pretreated with oral methadone . HCl. 44 29

The present study describes the effects of tetraethyl lead on various drug metabolizing enzymes in different tissues of the rat. Tetraethyl lead was administered intraperitoneally to rats (250 mumol/kg) on two consecutive days. The animals were killed on day 3. Tetraethyl lead-treatment decreased the concentration of hepatic cytochrome P-450 (to 45 per cent of the control), the hepatic activity of aryl hydrocarbon hydroxylase (to 41 per cent of the control) and ethoxycoumarin deethylase (to 45 per cent of the control). Epoxide hydratase activity was enhanced in the liver (1.3-fold), kidney (3.3-fold), and small intestinal mucosa (4.7-fold). The activity of glutathione S-transferase decreased in the liver (to 69 per cent of the control) but increased in the kidney (1.5-fold) and small intestinal mucosa (1.7-fold). The glucuronidation of o-aminophenol was enhanced (2.2-fold) in the kidney of tetraethyl lead treated rats. It is concluded that exposure to tetraethyl lead brings about widespread changes in the ability of mammals to detoxify foreign compounds.
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PMID:Effects of tetraethyl lead on the activities of drug metabolizing enzymes in different tissues of the rat. 47 47

An in vitro assay for the determination of the activity of disopyramide-N-dealkylation was developed. This reaction was concluded to be catalyzed by the liver microsomal, cytochrome P-450 centered monooxygenase system. Phenobarbital enhanced the N-dealkylation of disopyramide four fold, and disopyramide itself 1.6 fold, whereas methylcholanthrene was without effect. Disopyramide also increased ethoxycoumarin deethylation 1.6 fold, and had a slight increasing effect on the activity of epoxide hydratase, but did not affect the activities of glutathione S-transferase or UDPglucuronosyltransferase.
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PMID:Induction of disopyramide N-dealkylation by phenobarbital and disopyramide in rat liver. 48 13

Rats and mice were exposed to the fumes of oxidative thermal degradation of polystyrene (350 degrees C). A decrease in the reduced glutathione (GSH) in both liver and lung was detected immediately after both the acute (mice, 3 h) and subacute (rats, 3 weeks) exposures were stopped. Later on an elevation in the amount of GSH due to the increased synthesis (rebound effect) could be seen. Cytochrome P-450 content in mouse liver was initially decreased after acute exposure, but the prolonged treatment doubled the amount of the P-450 hemoprotein in liver microsomes. After acute exposure 7-ethoxycoumarin 9-deethylase activity in mouse liver was doubled in 24 h. When the exposures were continued, this enhancement in ethoxycoumarin O-deethylase activity gradually disappeared. O-deethylase activity was also enhanced in rat liver and lung after subacute exposure. The exposures given had no effect on diphenyloxazole hydroxylase, and the effects on the conjugating enzymes (epoxide hydratase, UDPglucuronosyltransferase, glutathione S-transferase)) were insignificant in rat liver.
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PMID:Effects of thermal degradation products of polystyrene on drug biotransformation and tissue glutathione in rat and mouse. 73 18

With 8-(14)C-styrene oxide as substrate, specific glutathione S-transferase and epoxide hydrase activities were determined in subcellular fractions of liver, lungs, kidney, and intestinal mucosa from rabbit, rat, and guinea pig. Liver had the highest enzyme activities in each species. Rat and guinea pig had higher glutathione S-transferase activity in both liver and kidney than rabbit. Rat testis also had appreciable glutathione S-transferase activity. The perinatal development of epoxide hydrase and glutathione S-transferase was followed in liver and several extrahepatic tissues of fetal and neonatal guinea pigs and rabbits. The rates at which enzyme activities reached adult levels in the extrahepatic tissues differed from the liver in both species. Epoxide hydrase and glutathione S-transferases developed at different rates in each organ, demonstrating that the relative importance of these two detoxifying pathways for styrene oxide may shift before and after birth. The effects of pretreating male and female rats with phenobarbital (PB), 1,2,3,4-dibenzanthracene (DBA), pregnenolone-16alpha-carbonitrile (PCN), or 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on hepatic and extrahepatic epoxide hydrase and glutathione S-transferase activities toward styrene oxide were determined. PB increased both enzyme activities in liver of both sexes. PCN induced only glutathione S-transferase activity in female liver. Extrahepatic epoxide hydrase and glutathione S-transferase activities were unaffected except that TCDD doubled female renal epoxide hydrase activity and PB increased intestinal epoxide hydrase activity in both sexes. Styrene oxide biotransformation was studied in isolated, perfused rat liver and rabbit lung preparations. Conjugation with glutathione was a major metabolic pathway although significant amounts of diol were also formed in each instance. In rat liver, 27-40% of the administered styrene oxide was excreted via the bile mainly as S-(1-phenyl-2-hydroxyethyl)glutathione.
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PMID:Hepatic and extrahepatic metabolism of 14C-styrene oxide. 102 99

Intoxication of male and female mice with a single dose (300 or 600 mg/kg) of 1,1,2,2-tetrachloroethane (TTCE) resulted in significant decreases in cytochrome P-450 (to 58-73% of the control) and NADPH-cytochrome (P-450) c-reductase (to 29-35% of the control) in hepatic microsomes. This was accompanied by an alteration of mixed function monooxygenases stemming from the marked reduction (to 20-64% of the control) of several oxidative activities to selected substrates towards different P-450 isozymes (classes IA1, IA2, IIB1, IIE1 and IIIA). As phase II markers, epoxide hydrolase (approximately 35% loss), UDP-glucuronosyl transferase (approximately 42% loss) and to a lesser extent glutathione S-transferase (approximately 17% loss) were all affected. Also, the activity of delta-aminolevulinic (ALA) synthetase was decreased (approximately 57% of the control). On the contrary, heme oxygenase activity was increased (up to 35%) at the maximal dose tested. The decrease of P-450-function may be explained in terms of an alteration in the rate of heme biosynthesis and degradation, provoking a loss of heme content (approximately 33%) as well as of the direct inactivation of both P-450 and reductase. Because of increasing evidence on the involvement of free radical intermediates in the case of toxicity of haloalkanes, electron spin resonance spectroscopy (ESR) spin-trapping in vivo techniques were used to characterize the possible free radical species involved in the observed liver damage. The results obtained with the spin-trap N-benzylidene-2-methylpropylamine N-oxide (phenyl t-butylnitrone, PBN) provide evidence for the formation and trapping of the CHCl2CHCl free radicals. The detection of conjugated diene signals by means of second-derivative spectrophotometry, have enabled us to show that in vivo lipid peroxidation may be one of the main mechanisms responsible for TTCE hepatotoxicity.
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PMID:On the hepatotoxicity of 1,1,2,2-tetrachloroethane. 131 68

Cigarette smoking is the strongest risk factor for lung cancer, but genetically determined variations in the activities of pulmonary enzyme that metabolize tobacco-derived carcinogens may affect individual risk. To investigate whether these enzymes (e.g., CYP1A-related) can serve as markers for carcinogen-DNA damage, lung tissue specimens were taken during surgery from middle-aged men with either lung cancer or non-neoplastic lung disease. Phase I [aryl hydrocarbon hydroxylase (AHH), ethoxycoumarin O-deethylase (ECOD)] and phase II (epoxide hydrolase, UDP-glucuronosyltransferase, glutathione S-transferase) enzyme activities, glutathione and malondialdehyde contents were determined in lung parenchyma and/or bronchial tissues; some samples were also analyzed for DNA adducts, using 32P-postlabeling. The data were then analyzed for the following: a) differences in metabolic profiles between bronchial and parenchymal lung tissue; b) the effect of recent exposure to tobacco smoke on enzyme inducibility and benzo[a]pyrene metabolism; c) differences in enzyme inducibility between lung cancer and non-lung cancer patients; d) the effect of smoking on metabolism of mutagens in vitro; e) pulmonary DNA adduct levels and AHH activity in lung parenchyma of smokers and ex-smokers; f) lipid peroxidation products in lung tissue from lung cancer and non-lung cancer patients, as related to smoking habits and degree of airway obstruction; and g) prognostic value of AHH pulmonary activity in lung cancer patients. The results demonstrate a pronounced effect of tobacco smoke on pulmonary metabolism of xenobiotics and prooxidant state and suggest the existence of a metabolic phenotype at higher risk for tobacco-associated lung cancer.
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PMID:Carcinogen metabolism in human lung tissues and the effect of tobacco smoking: results from a case--control multicenter study on lung cancer patients. 133 22

The coordinated response of the major rat hepatic phase II xenobiotic-metabolizing enzymes following 3-day exposure to diaryl compounds was investigated. Four diaryl compounds containing heterocyclic nitrogen atoms elevated microsomal epoxide hydrolase activity from 2- to 4-fold. Equivalent compounds lacking the heteroatom, when given in the same dosing regimen (75 mg/kg, ig, daily for 3 days), did not induce this or any other drug-metabolizing enzyme activity. Epoxide hydrolase activity closely paralleled UDP-glucuronosyltransferase activity toward three aglycones: 4-nitrophenol (r = 0.87), morphine (r = 0.84), and 1-naphthol (r = 0.78). There was less correlation (r = 0.60) between epoxide hydrolase activity and both UDP-glucuronosyltransferase activity toward testosterone and cytosolic glutathione S-transferase activity. There was no correlation between microsomal epoxide hydrolase activity and cytochrome P-450 or the monooxygenase reaction (4-nitrophenol hydroxylase) preferentially induced by pyridine-containing compounds. Induction of rat hepatic microsomal epoxide hydrolase activity by some pyridine-containing compounds appears coordinately regulated with glucuronidation rather than oxidation enzymes.
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PMID:Concomitant induction of microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities by dipyridine compounds. 135 78


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