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

---

Query: EC:2.5.1.18 (glutathione S-transferase)
22,582 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of dietary administration of 0.5% ethoxyquin (EQ) on the in vivo induction of enzymes and effect on aflatoxin B1 (AFB1)-DNA binding in liver and the consequent in vitro metabolism of AFB1 by male Fischer F344 rat liver-derived fractions have been examined. EQ increased microsomal cytochrome P-450s, in particular those isozymes classed as phenobarbital inducible, and the in vitro rate of metabolism of AFB1. The formation of the presumed detoxified metabolites, aflatoxins M1 and Q1, was enhanced to a greater extent than was the formation of the active metabolite, aflatoxin B1-8,9 epoxide (assessed by the level of aflatoxin B1-8,9-dihydrodiol). Prolonged feeding with EQ was accompanied eventually by a reduction in the initially elevated cytochrome P-450 content, but this was not reflected in any significant decrease in the rate of AFB1 metabolism in vitro. EQ increased the glutathione S-transferase activity of the liver cytosol fractions as assessed with the model substrate 1-chloro-2,4-dinitrobenzene. The capacity of these fractions specifically to catalyze the conjugation of AFB1 with glutathione was induced to a far greater extent than was the conjugation of 1-chloro-2,4-dinitrobenzene. gamma-Glutamyl transpeptidase was induced in the periportal areas of the liver lobule. Reduced in vivo binding of [3H]AFB1 to DNA of liver and kidney was found to result from EQ treatment. It is concluded that the reduced hepatocarcinogenesis which results from feeding EQ simultaneously with AFB1 is due to the reduction in DNA-adduct formation which in turn is due at least in part to increased detoxifying metabolism in the microsomal, cytosolic, and plasma membrane compartments of the liver cells.
...
PMID:Metabolic basis for the protective effect of the antioxidant ethoxyquin on aflatoxin B1 hepatocarcinogenesis in the rat. 288 84

A previously validated small mammal trauma model, hindlimb ischemia secondary to infrarenal aortic ligation in the rat, was utilized to investigate the effects of traumatic injury on two of the major hepatic enzymes of detoxification, glutathione S-transferase and epoxide hydrolase. Hepatic cytosolic glutathione S-transferase activity toward a variety of substrates showed a 26-34% decrease at 24 hr after model injury. Hepatic microsomal epoxide hydrolase activity toward 1,2-epoxy-3-(p-nitrophenoxy)propane was diminished by 53% after model trauma. Both enzymatic activities toward styrene oxide were similarly depressed. The toxicological sequelae of these derangements were illustrated by administering a dose of styrene oxide (300 mg/kg, ip) which was below the threshold dose (350 mg/kg, ip) necessary to produce hepatotoxicity in control animals. Model trauma dramatically enhanced the hepatotoxic effects of the subthreshold dose, as well as the covalent binding of labeled styrene oxide to liver proteins. These findings indicate that traumatic injury renders the animal more susceptible to agents which are detoxified by glutathione S-transferase and epoxide hydrolase. Conversely, model trauma provided almost complete protection from the hepatotoxic effects of a standard dose (200 mg/kg, ip) of bromobenzene. This protection appeared to derive from a post-traumatic alteration of cytochrome P-450 subpopulations that decreased the formation of the potentially toxic 3,4-epoxide metabolite, despite an increase in the cytochrome P-448-mediated generation of the nontoxic 2,3-epoxide. For bromobenzene, the change in cytochrome P-450-mediated activation appeared quantitatively more significant in overall toxicity than the post-traumatic depression of detoxification pathways described above, leading to decreased toxicity in vivo. For other compounds, the combination of post-traumatic influences on cytochrome P-450/P-448 activity and epoxide hydrolase/glutathione S-transferase activities could lead to markedly enhanced toxicity.
...
PMID:Effects of model traumatic injury on hepatic drug metabolism in the rat. VI. Major detoxification/toxification pathways. 289 98

There is a varied distribution of airway epithelia throughout the respiratory tract that may explain the apparent differential susceptibility of respiratory tract tissues to carcinogens. The objective of this research was to characterize the distribution of xenobiotic metabolizing enzymes in the respiratory tract of the dog and to determine if regional variances in metabolic capability are associated with morphologic differences of surface epithelium among airways. Specific regions from one-half of the nasal, tracheal, bronchial, and pulmonary airways were excised and analyzed for the presence of xenobiotic metabolizing enzymes. Complementary halves of airways were fixed and processed for light microscopy. Substrates for different isozymes of cytochrome P-450, including benzo(a)pyrene, nitropyrene, ethoxycoumarin, and ethoxyresorufin and select Phase II enzymes were measured. The data for benzo(a)pyrene and nitropyrene were qualitatively similar in that there was high metabolic activity in certain regions of the nasal tissue (e.g. ethmoid turbinates) and in the intrapulmonary airway generations 3-18 compared with the major conducting airways (e.g. larynx, trachea, and bronchi). Most ethoxycoumarin O-deethylase activity was in the nasal region with much less activity observed in the major airways or the pulmonary airways. The specific activity of ethoxycoumarin O-deethylase in the ethmoid turbinates was, in general, 5-10 times that observed for the other portions of the nasal cavity sampled. Only the ethmoid turbinates showed evidence of ethoxyresorufin metabolism. Both epoxide hydrolase and glutathione transferase activity was higher in the various tissues of the nasal cavity and in the pulmonary airways compared with the major conducting airways. UDP-glucuronyltransferase was relatively evenly distributed throughout the respiratory tract.(ABSTRACT TRUNCATED AT 250 WORDS)
...
PMID:Regional distribution of xenobiotic metabolizing enzymes in respiratory airways of dogs. 289 39

The expression of A and P forms of glutathione S-transferase (GST-A and P), two cytochrome P-450 isoenzymes (P-450 PB3a and P-450 MC2), microsomal epoxide hydrolase (mEHb), glucose-6-phosphate dehydrogenase (G6PD) and gamma-glutamyltranspeptidase (gamma-GT) was compared in preneoplastic liver lesions and background parenchyma of F344 rats post-treated with butylated hydroxyanisole (BHA), ethoxyquin (EQ) or acetaminophen (AAP). These latter three compounds have been shown to inhibit hepatocarcinogenesis after initial treatment with N-ethyl-N-hydroxyethylnitrosamine (EHEN) and a significant decrease in the number of enzyme-altered foci and nodules positive for GST-P, GST-A, G6PD and gamma-GT and negative for P-450 PB3a, P-450 MC2 was associated with their administration. Whereas in the foci case the decrease was most prominent for non-discrete (heterogeneous) type lesions, the results of quantitation of nodules revealed a most significant alteration in the discrete homogeneously staining population. This indicates that BHA, EQ and AAP have the potential to inhibit the growth of the phenotypically stable lesions thought most likely to be the immediate precursors of hepatocellular carcinomas. The two anti-oxidants were associated with periportal increase of all enzymes investigated, whereas AAP induced GST species and mEHb in the perivenular zone. Irrespective of slightly elevated enzyme levels in surrounding parenchyma, mEHb antibody binding levels within lesions showed a reciprocal shift from positive to negative in rats treated with BHA, EQ and AAP.
...
PMID:Effect of modifying agents on the phenotypic expression of cytochrome P-450, glutathione S-transferase molecular forms, microsomal epoxide hydrolase, glucose-6-phosphate dehydrogenase and gamma-glutamyltranspeptidase in rat liver preneoplastic lesions. 289 90

The effects of N-benzylimidazole on hepatic microsomal and cytosolic drug-metabolizing enzymes were compared to the effects produced by phenobarbital, beta-naphthoflavone, a polycyclic aromatic hydrocarbon, and Aroclor 1254, a polychlorinated biphenyl mixture. N-Benzylimidazole was a "high magnitude" inducer of male rat hepatic cytochrome P-450, inducing cytochrome P-450 over 3 times above control. N-Benzylimidazole exhibited mixed type induction of cytochrome P-450, producing both polycyclic aromatic hydrocarbon- and phenobarbital-type induction. There was no evidence of imidazole (isoniazid) type induction characteristics. Microsomes from rats treated with either Aroclor 1254 or N-benzylimidazole showed a common pattern of induction of the cytochrome P-450-dependent properties and glucuronosyltransferase activities, and the electrophoretic profiles of proteins were also similar. Cytosolic glutathione transferase activity was also induced similarly after treatment with the two agents.
...
PMID:N-benzylimidazole, a high magnitude inducer of rat hepatic cytochrome P-450 exhibiting both polycyclic aromatic hydrocarbon- and phenobarbital-type induction of phase I and phase II drug-metabolizing enzymes. 289 44

1. The comparative distribution of cytochrome P-450 monooxygenase system, glucuronyltransferase, glutathione S-transferase and N-acetyltransferase was studied in the liver, lung and kidney of young male sheep. 2. The sheep liver was characterized by a lack in glutathione S-transferase activity with isoniazid as substrate. 3. The oxidative drug metabolizing enzymes of lung were generally close to those of liver; benzphetamine N-demethylase and ethoxycoumarin O-deethylase were even found to be higher in lung (213 and 148%, respectively). 4. Pulmonary conjugative and both renal oxidative and conjugative systems accounted only for 9-38% of hepatic corresponding enzymes. 5. The enzyme determination in various sampling sites of the three organs, demonstrated the homogeneous distribution of all investigated monooxygenases and transferases in liver, lung and kidney of sheep.
...
PMID:A comparative study of some oxidative and conjugative drug metabolizing enzymes in liver, lung and kidney of sheep. 289 1

Previously we established that 'LEC rats' have displayed spontaneous fulminant hepatitis with severe jaundice, which progressed to liver cancer, and a single autosomal recessive gene is responsible for the cause of the diseases. The activities of drug metabolizing enzymes were assayed in livers from LEC and control (LEA) rats at 4 weeks and 3 months before the onset of liver cancer. At 4 weeks the cytochrome P-450 content of the LEC rat livers was 43% of the control (LEA) value. At 3 months the level was 65% of the control. Epoxide hydrolase, gamma-glutamyltranspeptidase and UDP-glucuronyltransferase activities were 2.6-, 6.9- and 2.4-times higher than those in the LEA rats at 4 weeks, respectively, while glutathione S-transferase activity was not significantly different between the two strains. The enzyme changes in the LEC rats are quite similar to those observed in hyperplastic foci and nodules in chemical carcinogenesis of hepatocytes.
...
PMID:Metabolic predisposition of a novel mutant (LEC rats) to hereditary hepatitis and hepatoma: alterations of the drug metabolizing enzymes. 290 Jul 2

Experiments were undertaken to examine the ability of selenium to protect against acetaminophen-induced hepatotoxicity and to examine possible mechanisms for this protective effect. Pretreatment of male, Sprague-Dawley rats with sodium selenite (12.5 mumol Se/kg, ip) 24 hr prior to acetaminophen administration produced a significant protection against the hepatotoxic effects of acetaminophen as assessed by a decrease in the plasma appearance of alanine aminotransferase and aspartate aminotransferase activities following acetaminophen. This was accompanied by an increase in the hepatic glutathione levels in selenium-treated animals and an inhibition in the decrease in hepatic glutathione content observed in animals receiving hepatotoxic doses of acetaminophen. Selenium pretreatment decreased the in vivo covalent binding of acetaminophen metabolites to hepatic protein, but did not alter hepatic microsomal cytochrome P-450 content or NADPH cytochrome c reductase activity, suggesting that selenium does not significantly alter the metabolism of acetaminophen to reactive electrophilic metabolites by the cytochrome P-450-dependent mixed-function oxidase enzyme system. Selenium produced an increase in the activity of gamma-glutamylcysteine synthetase which may account for the increased glutathione availability in selenium-treated animals and increased the activities of glutathione S-transferase and glucose-6-phosphate dehydrogenase. Examination of the urinary metabolite profile in selenium-treated animals revealed that the urinary excretion of acetaminophen and its metabolites was significantly increased over a 72-hr period. The increase occurred in the AAP-glucuronide metabolite while parent AAP and AAP-sulfate were actually decreased in selenium-treated rats. No change in recovery was observed in the AAP-glutathione or AAP-mercapturate urinary metabolites. While the glutathione conjugating system is enhanced by selenium treatment, amelioration of acetaminophen toxicity is most likely the result of enhanced glucuronidation which effectively diverts the amount of acetaminophen to be converted by the cytochrome P-450 system to the toxic metabolite.
...
PMID:Protective effects of selenium on acetaminophen-induced hepatotoxicity in the rat. 290 Nov 47

Purified vomitoxin was incorporated into the diet at a level of 20 ppm and fed to male Sprague-Dawley rats ad lib. for 90 days. Few clinical signs of toxicity were observed. Rats in the vomitoxin treatment group were less efficient in converting feed into body mass, but there was no feed refusal. Terminal body weight was reduced in the vomitoxin treatment group. There were no statistically significant effects on serum enzyme levels, haematological parameters or tissue lesions, or on liver detoxification systems, as reflected in levels of microsomal cytochrome P-450 or in glutathione S-transferase activity.
...
PMID:Subchronic toxicity of vomitoxin in Sprague-Dawley rats. 293 4

The present study was designed to prepare and characterize subcellular fractions from the head kidney of the Northern pike (Esox lucius), with special emphasis on the preparation of a microsomal fraction suitable for studying xenobiotic metabolism. The purity of the different fractions obtained by differential centrifugation as well as the recovery of different cell components was determined using both enzyme markers and morphological criteria. Finally, the subcellular distributions of several drug-metabolizing enzymes (NADPH-cytochrome c reductase, NADH-ferricyanide reductase, glutathione transferase, epoxide hydrolase) were determined. With the exception of NADPH-cytochrome c reductase, the subcellular distributions obtained here for drug-metabolizing and marker enzymes closely resembled those reported for rat liver. NADPH-cytochrome c reductase was apparently partially solubilized here from microsomal vesicles by an endogenous protease, which reduced its usefulness as a marker enzyme and raises questions concerning the measurement of activities catalyzed by the cytochrome P-450 system in these subfractions. In other respects the microsomal fraction prepared here from the pike head kidney seems well-suited for studies of drug metabolism.
...
PMID:Preparation and characterization of subcellular fractions from the head kidney of the Northern pike (Esox lucius), with particular emphasis on xenobiotic-metabolizing enzymes. 298 37


<< Previous 1 2 3 4 5 6 7 8 9 10

---