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)

1. The expression of P450 isoenzymes in foetal and neonatal hepatic microsomes was determined by measuring the metabolism of marker substrates and by studying the expression of P450 isoenzymes at the protein and mRNA level. 2. Monooxygenase activities were not measurable at day 10 of gestation, but shortly before birth (day 20 of gestation) and thereafter a surge in monooxygenase activities was observed using ethoxyresorufin, aniline, nitroanisole, aminopyrine, dimethylnitrosamine and aldrin as substrates. 3. In contrast, as early as day 10 of gestation, post oxidative drug metabolism was measurable, when assessed for reactions catalysed by UDP-glucuronyltransferase, glutathione S-transferase and epoxide hydrolase. 4. Microsomal proteins isolated from foetal/perinatal rats did not crossreact with antibodies raised to CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1, CYP3A1 and CYP4A1 at a protein loading of 3 micrograms total protein/well. 5. With the exception of CYP2E1 mRNA and CYP4A1 mRNA there was little evidence to suggest the expression of CYP1A1, CYP1A2 and CYP2A1 mRNA. 6. The mRNA of CYP2B1, CYP2C7 and CYP3A1 was not detectable in foetal/perinatal rat liver extracts at a loading rate of 10 micrograms total RNA. 7. Microsomal proteins isolated from neonatal rats crossreacted with antibodies raised to CYP2C6, CYP2E1, CYP3A1 and CYP4A1, albeit at varying intensities. 8. Concomitantly, CYP2A1, CYP2E1 and CYP4A1 mRNA transcripts were detectable in Northern blot hybridization experiments using neonatal rat liver RNA extracts.
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PMID:Expression of P450 isoenzymes during rat liver organogenesis. 828 35

The hepatic microsomal drug metabolism during pregnancy and lactation was studied. Four days post partum, the concentrations of cytochrome P450 and cytochrome b5 were reduced by 50% when compared with pregnant rats, at day 10 of gestation. Within this time period the N-demethylation of aminopyrine, the rate of aldrin epoxidation and the N-demethylation of demethylnitrosamine was reduced by 53, 74 and 21%, respectively. However, the rates of ethoxyresorufin-O-deethylation did not differ amongst both groups and the deethylation of 4-nitroanisole and the 4-hydroxylation of aniline was increased by 71 and 31%, respectively in lactating rats. Furthermore, the activities of UDP-glucuronyltransferase and glutathione S-transferase were increased by 21 and 27%, but those of epoxide hydrolase were reduced by 85%. Western immunoblot analysis of microsomal proteins obtained from pregnant and lactating rats shows that only proteins encoded by the genes of CYP2C6 and CYP3A1 are expressed at detectable levels, whereas the expression of CYP1A1, CYP1A2, CYP2A1, CYP2B1, CYP2E1 and CYP4A1 was not detectable in pregnant and lactating rats at a protein loading of 3 micrograms total protein per well. In contrast, in northern blot hybridization experiments, detectable amounts of mRNA of the above named isoenzymes were measurable, but at varying intensities. Based on the northern blot hybridization analysis, an approximate 4-fold and 3-fold increase in CYP2A1 mRNA and CYP3A1 mRNA was found, when lactating rats were compared with female controls or pregnant rats, at day 10 of gestation.
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PMID:Alterations in rat hepatic drug metabolism during pregnancy and lactation. 834 34

The induction by the central stimulant picrotoxin of hepatic drug-metabolizing enzymes was studied in rats. The hepatic content of P450 and the activity of benzphetamine N-demethylation increased gradually after administration of picrotoxin dissolved in drinking water (2 mg/mL), to three-times higher levels than the initial values at the third day of treatment. The increase in benzphetamine N-demethylase activity by picrotoxin was somewhat higher than the increase produced by phenobarbital. Supporting these results, immunoblot analysis showed that CYP2B1 and 2B2 proteins in the liver microsomes were increased by picrotoxin Picrotoxinin and picrotin, which are components of the picrotoxin molecule, had the same ability to induce the hepatic activity of benzphetamine N-demethylation. The liver microsomal activities of testosterone 16 alpha- and 16 beta-hydroxylation were enhanced significantly after treatment with picrotoxinin and picrotin. However, benzo[a]pyrene 3-hydroxylation, aniline 4-hydroxylation, and testosterone hydroxylations at the 2 alpha- and 7 alpha-positions were not increased by picrotoxinin and picrotin treatment. In addition to monooxygenase, significant induction of glutathione S-transferase activity for 1-chloro-2,4-dinitrobenzene and UDP-glucuronyltransferase activity for 4-hydroxybiphenyl and 4-nitrophenol was also observed by pretreatment of picrotoxin. These results clearly indicate that picrotoxin is an inducer of phenobarbital-inducible liver enzymes.
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PMID:Picrotoxin as a potent inducer of rat hepatic cytochrome P450, CYP2B1 and CYP2B2. 849 37

1. The effects of garlic oil (GO) on the expression of P4502E1, glutathione S-transferase (GST) and microsomal epoxide hydrolase (mEH) were assessed by metabolic activities, immunoblot and RNA blot analyses in the rat. 2. p-Nitrophenol (PNP) hydroxylase activity decreased in the hepatic microsomes isolated from rats treated with GO at 200 mg/kg b.w. by 10-30% as compared with control. Pyrazine-inducible P4502E1 expression was decreased by approximately 40% following concomitant treatment of animals with GO at the dose of 200 mg/kg from day 1 to 3 post-treatment, as evidenced by PNP hydroxylase activity. The rates of aniline hydroxylase and NDMA demethylase activities in GO-treated animals were consistent with those of PNP hydroxylase activity. Treatment of animals with 500 mg/kg GO resulted in suppression of P4502E1-mediated catalytic activities, as monitored by both PNP and aniline hydroxylase activities, whereas the effects at the dose of 1000 mg/kg were identical with those at 500 mg/kg b.w. 3. Immunoblot analyses of hepatic microsomes, using an anti-P4502E1 antibody, showed that GO minimally suppressed constitutive P4502E1 expression at 24, 48 and 72 h post-treatment at the daily doses from 200 to 1000 mg/kg b.w., as compared with vehicle-treated animals. Time-dependent pyrazine induction of P4502E1, however, was substantially blocked by concomitant treatment of animals with 200 mg/kg GO to the levels of control. Treatment at the dose of 1000 mg/kg failed to further suppress P4502E1 levels. GO treatment caused no changes in the levels of P4502E1 mRNA, as assessed by slot blot analyses. 4. Cytosol produced from the GO-treated rat showed approximately 40% increases in GST conjugating activity toward 1-chloro-2,4-dinitrobenzene, whereas mEH protein levels were 1.5-2.0-fold greater than control with similar increases in the mRNA levels noted. 5. These results demonstrate that GO suppresses inducible P4502E1 expression more significantly than constitutive expression, and that GO induces GST and mEH expression to a certain extent.
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PMID:Effects of garlic oil on rat hepatic P4502E1 expression. 857 58

The effects of chronic administration of aflatoxin B1 (AFB1) on liver drug metabolism enzymes were measured in New Zealand rabbits divided into three groups of 5 animals, each receiving over 5 days either arabic gum or AFB1 in arabic gum at a daily oral dose of 0.05 or 0.10 mg/kg. These treatments did not lead to any lethality in any of the treated groups, but the body weight gain was altered. Biochemical exploration of plasma components revealed a dose-dependent hepatotoxicity characterized by cytolysis and cholestasis. At 0.10 mg/kd/day of AFB1, significant decreases were observed in total liver microsomal cytochrome P450, several P450-dependent monooxygenase activities, all individual P450 isoenzymes levels analysed by Western-blotting and glutathione S-transferase activities. By contrast, at 0.05 mg/kg/day of AFB1, even though total cytochrome P450 was decreased by 30%, only P450 1A1 and 3A6 isoenzymes, and aniline hydroxylation, pentoxyresorufin O-depentylation, aminopyrine, erythromycin, ethylmorphine and dimethylnitrosamine N-demethylations were affected. In the same animal group, the only glutathione S-transferase accepting CDNB (1-chloro-2,4-dinitrobenzene) as substrate was decreased by 22%. UDP-glucuronyltransferase accepting p-nitrophenol as substrate was increased in both groups of animals (33-62%). The mechanisms that could contribute to the observed changes in drug metabolizing enzymes are discussed.
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PMID:Dose-related effect of aflatoxin B1 on liver drug metabolizing enzymes in rabbit. 864 16

Bitter melon (Momordica charantia), commonly known as karela, has been reported to have hypoglycemic, antiviral, antidiabetic, and antitumor activities. In the present study, we have investigated the effects of oral feeding of karela fruit juice on the hepatic cytochrome P450 (CYP) and glutathione S-transferase (GST) drug-metabolizing enzymes in the streptozotocin (STZ)-induced diabetic rat. Hepatic CYP contents, ethoxycoumarin-O-deethylase (ECOD), ethoxyresorufin-O-deethylase (EROD), aniline hydroxylase (AH), and aminopyrene N-demethylase (APD) activities were measured in control, diabetic, and karela juice fed animals. Diabetic rats exhibited a 50-100% increase in AH and EROD activities that was reversed by karela juice feeding. In addition, a decrease (17-20%) in the activities of APD and ECOD was observed in diabetic rat liver. Feeding of karela juice to the diabetic animals brought the level of APD close to that of control animals, while ECOD was further reduced to 60% of the control value. The cytosolic glutathione concentration was decreased in diabetic rats, and karela juice feeding normalized the effect. However, an increase (of 20-30%) in the GST activity was observed in both diabetic and karela juice fed rats. Western immunoblot analysis of CYP and GST isozymes exhibited a differential response during diabetes. The expression of CYP1A1, 2B1, 2E1, 3A4, and 4A2 in diabetes, while a decrease in GST mu was observed. Our results suggest that the changes in hepatic phase I and phase II drug-metabolizing enzyme activities in the STZ-induced diabetic animals may be associated with the altered expression of different CYP and GST isozymes. In addition, we have also observed that karela does not always reverse the effects on drug-metabolizing enzymes in STZ-induced diabetes.
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PMID:Effect of bitter melon (Momordica charantia) fruit juice on the hepatic cytochrome P450-dependent monooxygenases and glutathione S-transferases in streptozotocin-induced diabetic rats. 893 80

The ontogenic study of the hepatic biotransformation enzymes revealed the early development of both oxidative and conjugative enzymes in male chickens ranging in age from 3 to 12 weeks. Although the rate of microsomal cytochrome P450 reactions progressively increased during the first 9 weeks, it decreased thereafter. Furthermore, the proteins revealed by the antibodies to anti-cytochrome P450 1A2, 2B4, 2C7, and 3A4 appeared to be constitutively expressed. Hepatic monooxygenases were characterized by different developmental patterns. The demethylase activities increased progressively up to 9 weeks, then they declined, in 12 weeks reaching the activity level observed in 3-week-old chickens. In contrast, alkoxyresorufin O-dealkylases and benzopyrene hydroxylase activities continued to increase with age. Significant variability was noted for aniline hydroxylase. Among conjugation enzymes, UDP-glucuronyltransferase towards p-nitrophenol and isoniazid N-acetyltransferase activities increased with the age of the fowl, but with different profiles. Concerning glutathione S-transferase accepting 1-chloro-2,4-dinitrobenzene or 1,2-dichloro-4-nitrobenzene, the chickens aged from 3 to 9 weeks were less well developed in this enzyme than 12-week-old ones.
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PMID:Ontogenic development of drug-metabolizing enzymes in male chicken liver. 896 50

After 4 days of acetysal treatment (160 mg/kg body weight orally), the following were established: a higher acute toxicity of acetysal, an inducing effect on amidopyrin N-demethylase and analgin N-demethylase activity and increases in cytochrome P-450 and cytochrome b5 content. Aniline hydroxylase activity decreased, thiopental sleeping time was prolonged and UDP-glucuronyltransferase activity was not changed. Dexamethasone, at a dose of 5 mg/kg body weight p.o. for 4 days, did not change acetysal acute toxicity but at a dose of 100 mg/kg i.p. increased it. Thiopental sleeping time was shortened by dexamethasone (100 mg/kg i.p.) but was not changed by dexamethasone at 5 mg/kg p.o., alone or in combination. Dexamethasone at 5 mg/kg increased analgin N-demethylase and UDP-glucuronyltransferase activities, did not change cytochrome P-450 content and decreased aniline hydroxylase activity. The combination with 5 mg/kg dexamethasone increased the activity of amidopyrin N-demethylase, analgin N-demethylase and UDP-glucuronyltransferase and decreased those of amitriptyllin N-demethylase and aniline hydroxylase and cytochrome P-450 content. Ethylmorphine N-demethylase, benzphetamine N-demethylase, NADPH-cytochrome c reductase and glutathione S-transferase activities were not affected significantly by acetysal, dexamethasone or their combination. Hepatic carboxyl esterase was depressed by dexamethasone (5 mg/kg) and was increased by the combination. Lipid peroxidation was not changed by dexamethasone (5 mg/kg) but was decreased by acetysal and the combination.
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PMID:Effects of acetysal, dexamethasone and their combination on drug metabolizing enzyme systems in rat liver microsomes. 898 33

To investigate the detoxification of bromobenzene-induced hepatic lipid peroxidation by Oenanthe javanica DC, the hepatic lipid peroxide level and the activities of enzymes responsible for production and removal of epoxide were studied. The level of lipid peroxide elevated by bromobenzene was significantly reduced by the methanol extract (250 mg/kg) and persicarin (5 mg/kg). The methanol extract and persicarin administered daily over 4 weeks before intoxication with bromobenzene did not affect the activities of aminopyrine N-demethylase, aniline hydroxylase, and glutathione S-transferase. Epoxide hydrolase activity was decreased significantly by bromobenzene, which was restored to the control level by pretreatment with persicarin. However, the identical pretreatment with isorhamnetin and hyperoside did not change the enzyme activity or lipid peroxide level. The results suggest that the reduction of bromobenzene-induced hepatic lipid peroxidation by O. javanica under our experimental conditions is effected through enhancing the activity of epoxide hydrolase, an enzyme removing bromobenzene epoxide. In addition, the bioactive component of this plant responsible for the detoxification of bromobenzene, at least in part, is thought to be persicarin.
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PMID:Protective effect of Oenanthe javanica on the hepatic lipid peroxidation in bromobenzene-treated rats and its bioactive component. 900 Aug 78

The systemic toxicity of benzothiophene, a sulfur-containing heterocyclic present in petroleum, coal, and their derived products, was studied in male rats following short-term oral exposure. Male Sprague-Dawley rats (130 +/- 20 g) (n = 5 per dose group) were treated with benzothiophene by gavage at dosages of 0, 2, 20 or 200 mg/kg/d for 21 d. In another study, male rats were treated with 0, 100, or 500 ppm benzothiophene via the diet for 28 d. In the gavage study, the 200 mg/kg/d rats showed depressed weight gain, increased relative liver and kidney weights, decreased relative thymus weights, and elevated levels of serum gamma-glutamyltransferase (gamma-GT), hepatic aniline hydroxylase (AH), aminopyrine N-demethylase (APDM), pentoxyresorufin O-dealkylase (PROD), glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT) activities. A 4.5-fold increase in urine volume on d 14-21 and a transient, 4-fold increase in urinary ascorbic acid on d 1 were also detected. No treatment related changes in urinary N-acetylglucosaminidase (NAGA) activity were observed. Benzothiophene residues were not detected in adipose tissue, liver, and serum of rats in the 200 mg/kg rats, but a small quantity was detected in the urine. In the diet study, animals fed the 500 ppm diet had increased absolute and relative liver weights, elevated AH, APDM, and GST activities, decreased red blood cell count, and minor increases in serum urea nitrogen and glucose. In summary, benzothiophene produced adverse effects in male rats that included increased relative liver and kidney weights and increased urine output. Benzothiophene also caused increases in hepatic drug metabolizing enzyme activities of a phenobarbital type and a transient elevation in urinary ascorbic acid.
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PMID:Effects of benzothiophene on male rats following short-term oral exposure. 901 32


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