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)

Fruits and vegetables or their natural constituents which increase detoxication enzymes and/or reduce activating enzymes are considered as good candidates to prevent chemically-induced carcinogenesis. In this study, rats were fed a diet supplemented with 20% onion powder for 9 days. Several cytochrome P450 (CYP)s enzymes (CYP 1A, 2B, 2E1, 3A), which are involved in carcinogen activation, were determined by measuring their enzyme activities using specific substrates. In addition, phase II enzymes activities such as UDP-glucuronosyltransferase (UGT) and glutathione S-transferase (GST), involved in detoxication of carcinogens, were measured. Protein levels of CYPs and GST A1/A2, A3/A5, Ml, M2 and P1 were measured using antibodies in Western blots. Consumption of onion induced CYP 1A and CYP 2B activities while it decreased CYP 2E1 activity. This later modification was accompanied by a decrease of CYP 2E1 levels. The same dietary treatment caused a slight increase of the total GST activity. The relative proportions of GST subunits were modified. GST Al/A2 subunits were increased while GST A3/A5 and GST M2 subunits were decreased and GST M1 and P1 were not modified. Onion consumption also increased p-nitrophenol UGT activity. Taken together, these results suggest that the decrease of CYP 2E1 and the increase of phase II enzymes by onion can afford protection against some carcinogens, while the decrease of some GST subunits could increase the genotoxic effects of other chemicals. The modulating effect of onion could be ascribed to alk(en)yl polysulphides and/or glycosides of flavonols, which were identified in the onion powder.
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PMID:Effect of onion consumption by rats on hepatic drug-metabolizing enzymes. 1152 36

There is growing interest in the potential health benefits of tea, including the anticarcinogenic properties. We report here that white tea, the least processed form of tea, is a potent inhibitor of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP)-induced colonic aberrant crypts in the rat. Male Fischer 344 rats were treated for 8 wk with white tea (2% wt/vol) or drinking water alone, and on alternating days in experimental Weeks 3 and 4 the animals were given PhIP (150 mg/kg body wt p.o.) or vehicle alone. At the end of the study there were 5.65 +/- 0.81 and 1.31 +/- 0.27 (SD) aberrant crypt foci per colon in groups given PhIP and PhIP + white tea, respectively (n = 12, P < 0.05). No changes were detected in N-acetyltransferase or arylsulfotransferase activities compared with controls, but there was marked induction of ethoxyresorufin O-deethylase, methoxyresorufin O-demethylase, and UDP-glucuronosyltransferase after treatment with white tea. Western blot revealed corresponding increases in cytochrome P-450 1A1 and 1A2 proteins. Enzyme assays and Western blot also revealed induction of glutathione S-transferase by white tea. There was less parent compound and 4'-hydroxy-PhIP but more PhIP-4'-O-glucuronide and PhIP-4'-O-sulfate in the urine from rats given PhIP + white tea than in urine from animals given carcinogen + drinking water. The results indicate that white tea inhibits PhIP-induced aberrant crypt foci by altering the expression of carcinogen-metabolizing enzymes, such that there is increased ring hydroxylation at the 4' position coupled with enhanced phase 2 conjugation.
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PMID:Inhibition by white tea of 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine-induced colonic aberrant crypts in the F344 rat. 1209 35

Bisphenol A (BPA), an environmental estrogen derived from the plastic industry, was given orally via incorporation into the food of 30 male and female polecats at 3 different doses (10, 50, or 250 mg/kg body weight/day) for 2 wk with 10 animals acting as controls. Several hormone levels in the plasma were determined as well as the activities of the phase I and II biotransformation enzymes 7-ethoxyresorufin O-deethylase (EROD), cytosolic glutathione S-transferase (GST), and UDP-glucuronosyltransferase (UDPGT). BPA did not cause any macroscopic effects on body mass or the health of the animals. UDPGT and GST activities increased significantly in direct correlation with increasing BPA exposure in females and UDPGT increased in a dose-related manner in males. There was no change in the plasma T4 and testosterone concentrations of the males with increasing BPA exposure. Discriminant analysis indicated that the group receiving 10 mg BPA/kg body weight/d was not different from the control group but the groups receiving 50 and 250 mg/kg body weight/d were different from the control group. This suggests physiological changes in the groups receiving 50 or 250 mg BPA/kg body weight/d.
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PMID:In vivo effects of bisphenol A on the polecat (mustela putorius). 1213 37

A lower rate of colon cancer was observed in consumers of coffee with a high content of the diterpenes Kahweol and Cafestol (K/C). In animal models, K/C have been found to protect against the mutagenic/carcinogenic effects of compounds such as 2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (PhIP), aflatoxin B1, and 7,12-dimethylbenz[a]anthracene. Thus far, such chemoprotection by K/C has been attributed to modifications of xenobiotic metabolism, e.g. enhanced detoxification by UDP-glucuronosyltransferase (UDPGT) and/or glutathione transferase (GST). In the present study, we investigated the potential of several coffee-related treatments (K/C [1:1], Cafestol-alone, Turkish coffee) to modify the expression level of the DNA repair protein O(6)-methylguanine-DNA methyltransferase (MGMT) which is involved in the reversal of the precarcinogenic DNA damage O(6)-alkylguanine induced by alkylating agents. The results show that, in the male F344 rat, K/C and Cafestol increase hepatic MGMT in a dose-dependent manner up to a maximum of 2.6-fold at 0.122% K/C in the feed. Turkish coffee led to enhancements of up to 16%, the more moderate increase being associated with the lower estimated K/C intake through the beverage. In the livers of the rats receiving Turkish coffee, we also found 10-30% increases in several GST-related parameters (overall GST, GST-pi, glutathione, gamma-glutamylcysteine-synthetase) and a two-fold increase in UDPGT activity. Dose-response studies with K/C revealed that MGMT increased in parallel with three of the four GST-related parameters whereas the dose-response curves of UDPGT and of GST-pi activity displayed a steeper slope. Increased expression level of MGMT may extend the antimutagenic/anticarcinogenic potential of coffee components to protection against DNA alkylating agents.
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PMID:Coffee and its chemopreventive components Kahweol and Cafestol increase the activity of O6-methylguanine-DNA methyltransferase in rat liver--comparison with phase II xenobiotic metabolism. 1251 12

The aim of this study was to investigate the chemopreventive effects of widely consumed cruciferous vegetables, namely Brussels sprouts and red cabbage towards 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced preneoplastic lesions [liver glutathione-S-transferase placental positive (GST-P(+)) foci and colonic aberrant crypt foci (ACF)]. Male F344 rats were treated with IQ (100 mg/kg bw/g) on 10 alternating days and received drinking water supplemented with Brussels sprouts and red cabbage juices (5% v/v) before and during the carcinogen treatment. From each vegetable two different cultivars were tested. Brussels sprouts reduced the frequency of IQ-induced aberrant foci in both organs (41-52% in the colon and 27-67% in the liver). Also, Brussels sprouts drastically diminished (85-91%) the size of liver GST-P(+) foci, but no such effect was seen in the colon. With red cabbage, the size of liver GST-P(+) foci was markedly reduced (41-83%) whereas the foci frequency was only moderately decreased (19-50%). No protection was seen in the colon after treatment with red cabbage. Cooking (10 min, 100 degrees C) of the vegetables had no influence on their protective effects. The stronger chemoprotective effects of Brussels sprouts may be due to the fact that the overall glucosinolate contents were substantially (2-3-fold) higher than those of the cabbage cultivars, but it was not possible to attribute the reduction of preneoplastic lesions to specific glucosinolates. The activities of hepatic UDP-glucuronosyltransferase form 2 (UDPGT-2) and cytochrome P4501A2 were increased by both vegetables. The induction effect of Brussels sprouts on the activity of UDPGT-2 was more marked than that of the red cabbage cultivars, suggesting that increased glucuronidation of IQ may account for the reduction of the preneoplastic lesions. Our findings support the assumption that Brassica vegetables protect against the carcinogenic effects of heterocyclic amines.
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PMID:Chemoprevention of 2-amino-3-methylimidazo[4,5-f]quinoline (IQ)-induced colonic and hepatic preneoplastic lesions in the F344 rat by cruciferous vegetables administered simultaneously with the carcinogen. 1258 75

This article describes the development and use of assay models in vitro (genotoxicity assay with genetically engineered cells and human hepatoma (HepG2) cells) and in vivo (genotoxicity and short-term carcinogenicity assays with rodents) for the identification of dietary constituents which protect against the genotoxic and carcinogenic effects of heterocyclic aromatic amines (HAs). The use of genetically engineered cells expressing enzymes responsible for the bioactivation of HAs enables the detection of dietary factors that inhibit the metabolic activation of HAs. Human derived hepatoma (HepG2) cells are sensitive towards HAs and express several enzymes [glutathione S-transferase (GST), N-acetyltransferase (NAT), sulfotransferase (SULT), UDP-glucuronosyltransferase (UDPGT), and cytochrome P450 isozymes] involved in the biotransformation of HAs. Hence these cells may reflect protective effects, which are due to inhibition of activating enzymes and/or induction of detoxifying enzymes. The SCGE assay with rodent cells has the advantage that HA-induced DNA damage can be monitored in a variety of organs which are targets for tumor induction by HAs. ACF and GST-P(+) foci constitute preneoplastic lesions that may develop into tumors. Therefore, agents that prevent the formation of these lesions may be anticarcinogens. The foci yield and the sensitivity of the system could be substantially increased by using a modified diet. The predictive value of the different in vitro and in vivo assays described here for the identification of HA-protective dietary substances relevant for humans is probably better than that of conventional in vitro test methods with enzyme homogenates. Nevertheless, the new test methods are not without shortcomings and these issues are critically discussed in the present article.
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PMID:Development and application of test methods for the detection of dietary constituents which protect against heterocyclic aromatic amines. 1262 16

The effects of benzo[a]pyrene (B[a]P) on some drug-metabolizing and antioxidant systems in liver, lung, and stomach were investigated in normal and protein malnutrition (PM) rats. PM significantly inhibited tissue glutathione (GSH) content and increased hepatic lipid peroxidation. Cytochrome P450 isoform CYP1A1 was significantly increased in various tissues (42-73%). Also, lung glutathione S-transferase (GST) activity was significantly decreased (19%) in PM rats. On the other hand, B[a]P significantly induced tissue GSH of control and PM rats. Also, hepatic lipid peroxidation were significantly increased in control rats treated with B[a]P. Superoxide dismutase (SOD) activity was decreased by B[a]P treatment in PM rat stomach. B[a]P significantly induced both quinone reductase (QR) (in all tissues) and hepatic GST of control and PM rats. GST activity in PM rat liver was significantly higher than that of control rat liver after B[a]P treatment. Also, B[a]P induced hepatic CYP1A1 by 32-fold and 27-fold (P < or = 0.05) in control and PM rats, respectively. Stomach and hepatic UDP-glucuronosyltransferase activities were significantly decreased (34%) and increased (74%), respectively by B[a]P in PM rats. The results suggest that PM status has a modifying effect on the response of some antioxidant and metabolizing systems to a well-known carcinogen risk.
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PMID:Effects of benzo[a]pyrene on tissue activities of metabolizing enzymes and antioxidant system in normal and protein-malnourished rats. 1271 40

Tannic acid, a naturally occurring plant polyphenol, was shown to decrease the mutagenicity and/or carcinogenicity of several amines derivatives and polycyclic aromatic hydrocarbons in rodents. The aim of this study was to evaluate the effect of tannic acid on the activities of murine cytochrome P450 and phase II enzymes. The activities of ethoxyresorufin-O-deethylase (EROD), methoxyresorufin-O-demethylase (MROD), p-nitrophenol hydroxylase (PNPH), glutathione S-transferase (GST), UDP-glucuronosyltransferase (UDPGT) and NAD(P)H:quinone oxidoreductase (NQO1) were measured in the liver and kidney microsomes of female Swiss mice treated intraperitoneally (i.p.) with tannic acid in the dose range of 20-80 mg/kg. At the highest dose, tannic acid decreased the activities of EROD and MROD by 25-28% in mouse liver, while the activity of both hepatic and renal PNPH was reduced by approximately 50% as result of treatment. Moreover, Western blot analysis with CYP2E1 specific antibody showed a significant decrease in the levels of hepatic CYP2E1 in tannic acid treated animals. This polyphenol affected also the phase II enzymes in both tissues examined. The activity of GST was elevated in kidneys, but reduced in livers of the animals treated with tannic acid. The most striking effect was the inhibition of hepatic NQO1. The effect was dose dependent and almost 90% inhibition was observed after the treatment with tannic acid at the dose of 60 and 80 mg/kg. The same treatment caused the approximately 60% inhibition of renal NQO1. These results indicate that tannic acid, beside of scavenging active metabolites of chemical carcinogens, can change their metabolism by modulating the enzymes involved in xenobiotics activation and/or detoxification pathways.
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PMID:The effects of tannic acid on cytochrome P450 and phase II enzymes in mouse liver and kidney. 1274 24

Gastrointestinal tumours are among the most common malignancies in Western society, the majority of which are associated with dietary and lifestyle factors. Many dietary or lifestyle factors have been identified which may have toxic or carcinogenic properties. However, several dietary compounds also able to reduce gastrointestinal cancer rates in both humans and animals have been characterized. Though the exact mechanism leading to the anticarcinogenic action of these compounds is not fully known, it has been demonstrated that this chemopreventive capacity may be due to elevation of the glutathione S-transferase detoxification enzymes. Here we have investigated the effect of several anticarcinogens on the gastrointestinal UDP-glucuronosyltransferase (UGT) enzymes. Diets of male Wistar rats were supplemented with ellagic acid, ferulic acid, Brussels sprouts, quercetin, alpha-angelicalactone, tannic acid, coumarin, fumaric acid, curcumin and flavone, separately, and combinations of alpha-angelicalactone and flavone. Hepatic and intestinal (proximal, mid and distal small intestine and colon) UGT enzyme activities were quantified using 4-nitrophenol and 4-methylumbelliferone as substrates. All anticarcinogens tested increased UGT enzyme activity with both substrates, at one at least of the five different sites investigated. alpha-Angelicalactone, coumarin and curcumin showed enhanced UGT enzyme activities at all five sites. Both small and large intestinal UGT enzyme activities were increased by quercetin, alpha-angelicalactone, coumarin, curcumin and flavone. Except for tannic acid, all agents induced hepatic UGT enzyme activity. Furthermore, dietary administration of alpha-angelicalactone and flavone, given individually or in combination, enhanced the UGT detoxification system in the liver and, to a lesser extent, in intestine. In conclusion, induction of gastrointestinal UGT enzyme activities after consumption of dietary anticarcinogens may contribute to a better detoxification of potentially carcinogenic compounds and subsequently to the prevention of gastrointestinal cancer.
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PMID:Induction of rat hepatic and intestinal UDP-glucuronosyltransferases by naturally occurring dietary anticarcinogens. 1286 20

Wild carp, Cyprinus carpio, were sampled in January and March 2000 in a section of the Anoia River (NE Spain) known to be polluted by estrogenic compounds. At each sampling time, three groups were distinguished: (1) apparently normal males; (2) apparently normal females; and (3) affected fish. The latter were characterized by the simultaneous development of male and female tissue in their gonads at a macroscopical level (six out of 31 fish sampled at this particular point), or testicular atrophy (three out of 31). Plasmatic and hepatic vitellogenin (VTG) levels and plasma testosterone (T) and estradiol (E2) were measured to observe the particular estrogenic response of the affected fish. Moreover, the response in the xenobiotic metabolizing capacity in liver was tested. This involved the analysis of mixed function oxygenase (MFO) system such as: total cytochrome P450 content, NAD(P)H cytochrome c reductases and the associated CYP1A1, EROD activity. Also, glutathione S-transferase (GST) and UDP-glucuronosyltransferase (UDPGT) as detoxifying enzymes were measured. Our results showed: (1) a highly variable VTG content in all fish groups; (2) an increase in sex hormones content in March for the female group; and (3) an enhanced xenobiotics metabolism in the affected fish group, measured as total cytochrome P450, EROD activity in the January survey and cytosolic GST in March. The observed increase in VTG, sex hormones and in most of the enzymatic activities from January to March that could also be attributed to higher water temperature.
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PMID:Feminization of wild carp, Cyprinus carpio, in a polluted environment: plasma steroid hormones, gonadal morphology and xenobiotic metabolizing system. 1455 96


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