Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:Q8NEX9 (reductase)
 26,410 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats were treated with doxorubicin (2.5 mg/kg body wt, iv) once a week for 8 weeks. Alpha-Tocopherol (400 mg/kg body wt/day) was co-administered orally for 2 months. Cytochrome-P450 (Cyt-P450) and Cytochrome-b5 (Cyt-b5) levels decreased significantly in doxorubicin treated rats. Significant decreases were observed in glucose-6-phosphatase, Cyt-P450 and Cyt-b5 reductase activities. In vitro lipid peroxidation study showed that alpha-tocopherol significantly minimises the lipid peroxide formation by doxorubicin. There was a significant change in microsomal cholesterol and phospholipid levels. Alpha-Tocopherol co-administration reduced the alterations in xenobiotic metabolising system and microsomal lipid levels. The results were discussed with reference to drug metabolising enzymes, lipid peroxidation and antioxidant nature of alpha-tocopherol.
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PMID:Effect of alpha-tocopherol on doxorubicin-induced changes in rat liver and heart microsomes. 176 24

Cytochrome P450IIE1 (IIE1) is a microsomal xenobiotic-activating enzyme that is inducible not only by various chemical agents but also by fasting and diabetes. Using a rat model that mimics human obesity, we have found that hepatic IIE1 levels are also increased by this common clinical disorder. Liver microsomes from rats made obese by feeding with an energy-dense diet displayed elevated aggregate P450 content (+28%) and enhanced catalytic activities associated with IIE1, including low-Km N-nitrosodimethylamine demethylation (+66%), aniline hydroxylation (+52%), p-nitrophenol hydroxylation (+170%), and acetaminophen-cysteine conjugate formation (+28%). In contrast, obesity had no significant effect on cytochrome b5 content, P450 reductase activity, benzphetamine demethylation, or erythromycin demethylation, with the latter two reactions being linked with rat IIC11 and IIIA1, respectively. The enhancement of IIE1-dependent drug-metabolizing activities noted in liver microsomes from obese rats was paralleled by a similar increase (111%) in hepatic IIE1 protein content in these animals, as assessed on immunoblots developed with anti-hamster IIE1 IgG. Anti-IIE1-inhibitable rates of microsomal p-nitrophenol metabolism, a reaction highly correlated with IIE1 content (r = 0.88, p less than 0.01), were over 3-fold higher in obese rats than in nonobese controls, providing additional evidence for the obesity-related increase of hepatic IIE1. The induction of IIE1 by the pathophysiological condition of obesity may provide a biochemical basis for the increased incidence of occult liver disease and certain cancers noted in obese individuals.
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PMID:Induction of cytochrome P450IIE1 in the obese overfed rat. 200 76

The ability of doxapram (20 mg/kg, i.p. daily for 5 days) to induce hepatic cytochrome P-450 and xenobiotic metabolism was examined in male mice. Compared with the control values, the doxapram treatment significantly increased the amount of cytochrome P-450, and activities of aminopyrine N-demethylase, ethylmorphine N-demethylase and meperidine N-demethylase. In contrast, there were no changes in the activities of aniline hydroxylase, 7-ethoxycoumarine deethylase, NADPH-cytochrome c reductase and NADH-ferricyanide reductase, and cytochrome b5 content. These data show that there is a substrate specificity in the ability of doxapram to induce the hepatic drug metabolism in male mice.
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PMID:Induction of hepatic cytochrome P-450 and drug metabolism by doxapram in the mouse. 205 44

The localization of cytochrome P-450 dependent monooxygenase system in particular organs as well as in cellular structures has been presented. Attention was paid to microsomal, mitochondrial (inner membrane), nuclear (nuclear envelope), nucleolar localization of the system. In the liver cytochrome P-450 dependent monooxygenases occur in their maximum concentration, clustering in hepatocytes of the III acini zones. Cytochrome P-450 contents and the activity of its reductase gradually decrease in cells of the II and I zones. In the nephron the system under consideration also occurs in mitochondria and microsomes especially within the main nephron, that is, in the proximal convoluted tubules and in straight tubules. It has been estimated that the metabolic potential of the system does not exceed 15-20% of its hepatic potential. In the lungs which are an important pathway of xenobiotic penetration, cytochrome P-450 is found in Clara cells of the bronchioli, macrophages, II type alveolocytes and in the cells of endothelial blood vessels. In the alimentary tract the maximal concentration of the system in the proximal segment of the small intestine and its gradual reduction towards the rectum have been noted. In the villi and intestinal folds, enterocytes located on the peaks of the mentioned structures are characterized by the highest contents and activity of biotransformatic enzymes. The localization and role of the system in the placenta, elastic vessels, brain and prostatic gland have also been discussed.
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PMID:[Systemic localization of mixed function oxidases]. 209 90

The hepatic glutathione (GSH) system and the influences of xenobiotics have been reviewed. Key steps in the regulation of hepatic GSH are GSH biosynthesis, the GSH-peroxidase/reductase cycle, the cystathionine pathway, and the carrier-mediated export processes. Influences of xenobiotics on these different pathways are discussed. Xenobiotics may lead to liver injury after biotransformation to highly reactive electrophilic metabolites (mainly cytochrome P-450 mediated), which easily conjugate with GSH, thus producing GSH depletion. This GSH depletion and probably an additional loss of protein sulfhydryl groups cause a disturbance of the intracellular calcium homeostasis which leads to an irreversible cell injury. The different acinar distribution of cytochromes P-450 and of GSH and GSH-related detoxication pathways points to a greater susceptibility of perivenous hepatocytes to xenobiotic-induced damage. Also, the intracellular compartmentation of GSH is important for the understanding of hepatocellular injury induced by several xenobiotics.
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PMID:The hepatic glutathione system--influences of xenobiotics. 219 11

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.
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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

The present studies were aimed at evaluating the suitability of the differentiated Reuber hepatoma cells H4IIEC3/G- for monitoring permanent damage to the DNA caused by hepatotrophic chemicals. First we determined the profile of xenobiotic metabolizing enzymes. The cells expressed various cytochrome P-450-dependent monooxygenases, UDP-glucuronosyl-, phenol sulpho- and glutathione S-transferase, cytochrome c (P-450) reductase and carboxylesterases. We then established the conditions for genotoxicity testing in H4IIEC/G- cells. Induction of resistance against 6-thioguanine and appearance of micronuclei served as indicators for mutagenicity and clastogenicity, respectively. 6-Thioguanine-resistant H4IIEC3/G- cells were phenotypically stable for at least 30 cell cycles; recovery of 6-thioguanine-resistant cells was not significantly affected by the number of cells seeded for mutant selection up to at least 10(6) cells/100-mm dish; expression time of chemically induced mutants was 12-15 days; a period of 24 h after treatment appeared to be sufficient to allow for the formation of micronuclei. Finally we tested the genotoxic effects of promutagens which are typically activated or inactivated in liver. Aflatoxin B1, N-nitrosodiethylamine and cyclophosphamide were genotoxic to H4IIEC3/G- cells at concentrations of 10-30 nM, 2-20 mM and 1 mM, respectively. N-Nitrosodimethylamine and benzo[a]pyrene were not or only weakly cytotoxic and genotoxic to the cells, but this appears most likely to be due to protective mechanisms rather than to lack of metabolic activation. The results indicate that differentiated hepatoma cells such as H4IIEC3/G- offer a means of studying the potential of chemicals for inducing permanent DNA damage in liver cells.
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PMID:Mutagenicity, clastogenicity and cytotoxicity of procarcinogens in a rat hepatoma cell line competent for xenobiotic metabolism. 304 89

alpha, beta-Unsaturated aldehydes are reactive and cytotoxic compounds which occur in the environment and are also formed in vivo. Many of these aldehydes have been reported to inhibit hepatic cytochrome P-450. Our laboratory has shown that trans,trans-muconaldehyde (a possible metabolite of benzene) as well as acrolein and crotonaldehyde, when added to hepatic microsomes, decreased cytochrome P-450 (measured spectrophotometrically). Additional studies showed that several alpha, beta-unsaturated aldehydes also inhibited hepatic microsomal NADPH-cytochrome c reductase. Acrolein, crotonaldehyde and trans,trans-muconaldehyde all decreased NADPH-cytochrome c reductase activity in vitro. Concentrations of 0.5, 1.0 and 1.5 mM acrolein decreased activity to 60, 26 and 11% of control respectively. Similar concentrations of trans,trans-muconaldehyde inhibited NADPH-cytochrome c reductase. Crotonaldehyde was a less effective inhibitor of this enzyme. Propionaldehyde, a saturated aldehyde, had no effect on NADPH-cytochrome c reductase activity. Time course experiments with acrolein over a period of 5-45 min suggest that the loss of NADPH-cytochrome c reductase activity is non-linear. The addition of reduced glutathione protected against the inhibition of reductase activity by acrolein. Formation of these aldehydes and their subsequent inhibition of these enzymes may have important consequences in xenobiotic metabolism.
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PMID:Inhibition of microsomal cytochrome c reductase activity by a series of alpha, beta-unsaturated aldehydes. 310 27

The influence of immunoregulating humoral thymus factor T-activin (fraction AFT-6) on the activity of xenobiotic metabolism enzymes (EMX) and cellular-dependent cytotoxicity was investigated in germ-free guinea-pigs. Germ-free and conventional animals were injected 5 micrograms of T-activin intraperitoneally, on 3 successive days. The control animals were injected a physiologic saline. A day after the last injection the animals were killed, and EMX and K cell activity was measured. It was found that EMX activity in germ-free animals was decreased. T-activin stimulated cytochrome P-450, NADP-cytochrome-C-reductase, glutathione-S-transferase, benzopyrene hydroxylase and epoxyhydrase activity. In conventional animals the activity of these enzymes remained unchanged under the influence of T-activin. K-cell activity in germ-free animals was decreased, as compared to conventional guinea-pigs. Under the influence of T-activin the parameter increased and stood at about 70% of normal values.
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PMID:[Change in immunological and biochemical parameters in germ-free animals in response to T-activin]. 311 31

Immunological indices and activity of xenobiotic metabolism enzymes in lymphocytes were studied on minipigs under normal conditions, under conditions of chronic alcoholic intoxication and after administration of anabol (an immunomodulator) to normal healthy animals and to animals with alcohol intoxication. Age-related differences with respect to the number of T-lymphocytes and activity of lymphocyte glutathione S-transferase were observed in the normal animals, the other indices such as activity of natural killer cells, K-cells, blast cell transformation with concanavalin A and activity of cytochrome c-reductase being independent of the age. Administration of anabol to healthy animals did not alter their immunoenzymatic status. Chronic alcohol intoxication was accompanied by development of secondary immune deficiency characterized by lower immunological indices and lower activity of xenobiotic metabolism enzymes in lymphocytes. Daily exposure to 0.8 g of anabol for 12 days at this background resulted in normalization of the above indices.
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PMID:[Cellular immunity and enzyme activity of xenobiotic metabolism in the lymphocytes of normal minipigs and in alcohol and anabol exposures]. 332 21


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