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 effects of neonatal exposure to diethylstilbestrol (DES) on hepatic activation/detoxication enzyme levels in the adult rat were investigated. Neonatal exposure of male rats to DES (DES males) decreased the endogenous levels of UDP-glucuronyltransferase as compared to control males. Female rats exposed neonatally to DES (DES females) had higher endogenous epoxide hydrolase and glutathione transferase activity levels than control females. Adult animals treated neonatally with DES also had altered metabolic potential following exposure to 3-methylcholanthrene and phenobarbital. The DES males treated in adulthood with 3-methylcholanthrene had higher benzo(a)pyrene hydroxylase activities and lower UDP-glucuronyl-transferase activity levels than did control males treated in adulthood with 3-methylcholanthrene. The DES males exposed in adulthood to phenobarbital had reduced cytochrome P-450 and glutathione transferase activity levels as compared with respective controls. The DES females treated in adulthood with 3-methylcholanthrene had lower benzo(a)pyrene hydroxylase and epoxide hydrolase activity levels than control females receiving 3-methylcholanthrene. The DES females challenged in adulthood with phenobarbital also had decreased benzo(a)pyrene hydroxylase, epoxide hydrolase, UDP-glucuronyltrasferase, and glutathione transferase activity levels as compared with respective controls. Our results demonstrated that neonatal exposure to DES changed the endogenous levels of specific hepatic enzymes and altered the metabolic response of these adult animals to a carcinogen and a drug.
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PMID:Altered activation/detoxication enzymology following neonatal diethylstilbestrol treatment. 314 25

After oral administration of rifampicin and 25-desacetylrifampicin, which is a major metabolite of rifampicin in man but not in rat, to male Wister rats for 7 days, hepatic microsomal cytochrome P450, cytochrome b5, and activities of aniline hydroxylase, aminopyrine demethylase, bilirubin-conjugating enzymes and supernatant glutathione S-transferase were measured. Rifampicin induced bilirubin UDP-glucuronyltransferase, bilirubin UDP-glucosyltransferase, bilirubin UDP-xylosyltransferase and glutathione S-transferase activities, but did not induce mixed function oxidase activities. No inductive effect of desacetylrifampicin on any enzymes was observed. Serum bilirubin increased till the third day, and decreased after 7 days of rifampicin treatment. Plasma clearances of indocyanine green and sulfobromophthalein showed a marked delay after 1 day and 7 days of rifampicin treatment. Induction of bilirubin-conjugating enzymes and glutathione S-transferase by rifampicin in rats was different from that in humans, in which selective induction of mixed function oxidase is reported to occur. This species difference does not seem to be derived from the species difference of rifampicin metabolism, because no effect of desacetylrifampicin was observed. These results suggested that in rats rifampicin directly inhibits the hepatic excretion of bilirubin, whereas it enhances bilirubin conjugation due to enzyme induction.
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PMID:Induction of rat liver bilirubin-conjugating enzymes and glutathione S-transferase by rifampicin. 316 72

The metabolism of hexamethylphosphoramide (HMPA), aminopyrine, ethoxycoumarin, ethoxyresorufin, and pentoxyresorufin, by the monooxygenase cytochrome P-450-dependent system, was studied in microsomes from nasal epithelial membranes and liver tissue of Sprague-Dawley rats. Nasal metabolism rates for the different substrates ranged from 9% of liver values for aminopyrine to 83% for ethoxycoumarin. HMPA-demethylase activity followed Michaelis-Menten kinetics in nasal mucosa microsomes but was biphasic in those from liver. SKF 525A, metyrapone, dioxolane and alpha-naphthoflavone (ANF), inhibitors of various P-450 monoxygenases, were examined with regard to inhibition of nasal and liver ethoxycoumarin deethylase. In addition, activity of epoxide hydrolase, glutathione S-transferase, DT-diaphorase and UDP-glucuronyltransferase (UDP-GT) in nasal tissue homogenates were investigated. These activities were generally lower than those present in the liver. Various attempts to increase the activity of oxidative enzymes in nasal tissue by PB, 3-MC and ethanol failed, 3-MC and PB doubled the microsomal UDP-GT and the epoxide hydrolase activities. The results together with data from the literature suggest that the balance between P-450 isozymes and detoxifying enzymes differs in the nose compared with the liver. The activities of these enzymes in nasal tissue of different strains of rats also varies substantially with implications regarding the metabolic fate and activation of inhaled xenobiotics.
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PMID:Biotransformation enzymes in nasal mucosa and liver of Sprague-Dawley rats. 321 44

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

Water solubility and non-toxic properties of ascorbic acid are taken as criteria for beneficial effects of large doses of the vitamin. In the present study, male guinea pigs, dosed daily with 15, 30 or 50 mg/100g body weight for 10 weeks, demonstrated no differences in effect on liver and lung weights, body growth and microsomal protein contents of liver and lung when compared with controls. When guinea pigs were fed excessive ascorbic acid, there was a small non-significant increase (p less than 0.05) in hepatic and pulmonary cytochrome P-450, and significant increase (p less than 0.05) in hepatic cytochrome b5 which was accompanied with a significant increase in arylhydrocarbon hydroxylase activity in the two organs. Activity of NADPH-dependent cytochrome c-reductase was decreased in liver and remained unaffected in lung and colon. Drug detoxifying enzymes responded in different ways to increased intake of ascorbic acid. Activity of UDP-glucuronyltransferase remained unchanged on feeding excessive ascorbic acid, whereas glutathione S-transferase was decreased significantly in liver and was unaltered in lung and colon. Reduced glutathione was decreased only in the lung. The observed changes in drug activating and detoxifying enzymes appear to be important from drug pharmacokinetics and carcinogenesis point of view.
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PMID:Effect of large doses of ascorbic acid on the hepatic and extra-hepatic drug-metabolizing enzymes in guinea pig. 380 Oct 39

The effects of food deprivation, carbohydrate restriction and ethanol consumption on the metabolism of eight volatile hydrocarbons (benzene, toluene, styrene, chloroform, carbon tetrachloride, 1,2-dichloroethane, 1,1-dichloroethylene and trichloroethylene) in rats were compared with the effects of enzyme induction by phenobarbital (PB), polychlorinated biphenyl (PCB) and 3-methylcholanthrene (MC) on the metabolism of these compounds. Although causing a marked increase both in microsomal protein and cytochrome p-450 contents, PB (80 mg/kg per day for three days) and PCB (a single dose of 500 mg/kg) induced only a limited range of enzyme activity: PB increased the metabolism of toluene, styrene, chloroform, carbon tetrachloride and trichloroethylene, and PCB only increased those of toluene, styrene and trichloroethylene. MC (20 mg/kg per day for three days) had no effect on the metabolism of any of the hydrocarbons studied. In contrast, food deprivation, carbohydrate restriction and three-week ingestion of ethanol (2.0 g/day), each enhanced the metabolism of all the hydrocarbons with little or no increase in microsomal protein and cytochrome P-450 contents. PB, PCB and MC treatments enhanced the activity of enzymes involved in conjugation reactions, UDP-glucuronyltransferase and glutathione S-transferase, whereas the dietary manipulation and ethanol consumption produced no significant effect on these enzymes. It is concluded that ethanol consumption. lowered carbohydrate intake and food deprivation affect the metabolism and toxicity of volatile hydrocarbons differently from PB, PCB or MC.
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PMID:Enhanced metabolism of volatile hydrocarbons in rat liver following food deprivation, restricted carbohydrate intake, and administration of ethanol, phenobarbital, polychlorinated biphenyl and 3-methylcholanthrene: a comparative study. 392 Aug 36

The ontogeny and endocrine regulation of sex-differentiated hepatic metabolism is mediated via the hypothalamic-pituitary axis. Using in vitro-in vivo systems, we demonstrate alterations in activity levels of six sex-differentiated enzyme systems in male rats bearing ectopic pituitary tumors after the injection of a pituitary cell line, C811RAP. Activity levels of hepatic glutathione S-transferase, UDP-glucuronyltransferase, and aryl hydrocarbon hydroxylase are reduced to activity levels of control females, while histidase, 5 alpha-reductase, and serum cholinesterase levels are increased to levels of control females, i.e. feminization of all of these enzymes. RIAs of testosterone, estrogen, FSH, and PRL are similar in tumor-bearing and control animals, but GH levels are significantly higher in tumor-bearing animals than in the controls. It is suggested that GH may be the pituitary factor responsible for the expression of sex-differentiated hepatic metabolism.
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PMID:Modulation (feminization) of hepatic enzymes by an ectopic pituitary tumor. 392 55

Effects of eight structurally closely related substituted urea herbicides were investigated on the induction of cytochrome P-450 dependent monooxygenase enzyme complex, as well as on two conjugating enzymes after short-term treatment of rats. Liver microsomal cytochrome P-450 content was induced approximately by 50%. Cytochrome P-450 dependent monooxygenase activities showed a great variety depending on the substrate and on the herbicide. Two-18-fold induction was detected with 7-ethoxycoumarin, while up to 8-fold induction was measured with benzo(a)pyrene. Aldrin epoxidase activities were increased up to 3-fold, and aminopyrine N-demethylase activities were only slightly different from the control level. UDP-glucuronyltransferase and glutathione S-transferase activities were enhanced up to 2-fold. The results indicate that chemical structure of the related substituted urea compounds, the number of halogen substituents on their phenyl group exert a strong influence on the induction of monooxygenases.
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PMID:Induction of rat hepatic drug metabolizing enzymes by substituted urea herbicides. 392 58

Young male C57BL mice were exposed nose-only to cigarette smoke 20 min/day for 8 weeks while maintained on diets containing 0, 5, and 100 ppm of vitamin E. Smoking had no effect on hepatic aryl hydrocarbon hydroxylase (AHH), UDP-glucuronyltransferase, glutathione S-transferase, parathion desulfurase, or parathion esterase activity. Lung AHH activity was increased in all smoke-exposed mice, although the increase was significantly less in animals maintained on the vitamin E-free diet. All mice on the vitamin E-free diet showed reduced lung AHH activity and increased hepatic lipid peroxidation. No other biotransformations tested were significantly altered by varying vitamin E concentrations alone or in combination with cigarette smoke. For all vitamin E diets, both the smoke-exposed and sham-treated mice gained significantly less weight than the control animals. This effect was attributed to stress induced by restraint of the animals within the smoking apparatus. The results of these experiments show that both cigarette smoke and vitamin E-deficient diets may affect xenobiotic metabolism but that the combination does not appear to alter markedly their individual effects or to induce ones not previously observed.
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PMID:Effects of cigarette smoke and dietary vitamin E levels on selected lung and hepatic biotransformation enzymes in mice. 406 31

Effects of an antioxidant, butylated (3-tert-butyl-4-) hydroxyanisole (BHA) on the induction of specific molecular forms of glutathione S-transferase (GST), UDP-glucuronyltransferase (UDP-GT) and other glutathione-related enzymes in rat liver were investigated. The development of gamma-glutamyl transpeptidase (gamma-GTP)-positive foci and hyperplastic nodules induced by diethylnitrosamine, 200 mg/kg i.p., followed by 0.02% N-2-fluorenylacetamide (FAA) in diet plus partial hepatectomy was inhibited by the administration of 0.75% BHA in the FAA-containing diet. Inhibition was reflected in decreased area of gamma-GTP-positive foci which correlated with a decrease in gamma-GTP activity measured biochemically. Under the present experimental conditions, total activities of GSTs, especially that of GST-A form, and of UDP-GTs, especially that of the late fetal form (o-GT), were markedly increased, together with glutathione levels in the whole liver, within one week after BHA administration. Without BHA administration the activities of GST-A and o-GT, as well as glutathione levels, were also increased by FAA treatment, primarily localized within gamma-GTP-positive foci. These results suggest that the induction of specific molecular forms of detoxicating enzymes either in enzyme-altered foci or in the whole liver may play an important role in determining the extent of development of preneoplastic nodules from initiated foci under the short term induction conditions used.
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PMID:Induction by butylated hydroxyanisole of specific molecular forms of glutathione S-transferase and UDP-glucuronyltransferase and inhibition of development of gamma-glutamyl transpeptidase-positive foci in rat liver. 614 73


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