Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:1.6.5.2 (NQO1)
 6,196 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Various aspects of the cardiotoxicity of the anthracycline derivative and antineoplastic drug daunorubicin were investigated using isolated and cultured cells from neonatal rat hearts as a model system. Treatment of the cells with concentrations of daunorubicin of the same order of magnitude as those used in chemotherapy was accompanied by marked toxic effects, e.g. a decreased or abolished contraction, and release of lactate dehydrogenase, pyruvate and oxidized glutathione to the medium. A decreased frequency of contraction appeared to be the most sensitive probe of daunorubicin toxicity, followed by release of pyruvate and oxidized glutathione/lactate dehydrogenase. Daunorubicin and/or its metabolites also bound to cellular protein and DNA. Exposure to daunorubicin was shown to be accompanied by a rapid induction of primarily DT-diaphorase and a slower induction of glutathione transferase. The latter observations are interpreted to indicate a protective role of quinone- and peroxide-metabolizing enzymes, respectively, and support the hypothesis that daunorubicin toxicity involves generation of free radical derivatives, which initiate lipid peroxidation. This conclusion is further substantiated by the demonstration that addition of daunorubicin leads to an increased oxygen consumption.
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PMID:Toxic effects of daunorubicin on isolated and cultured heart cells from neonatal rats. 398 1

The effect of the antineoplastic agent daunorubicin on beating heart cells from neonatal rats was investigated with respect to cell damage and induction of enzymes possibly involved in drug metabolism. Of the enzymes assayed DT-diaphorase and glutathione-S-transferase showed a two-to-four fold increase in activity: higher concentrations of daunorubicin inactivated glutathione-S-transferase. Daunorubicin toxicity increased in the presence of dicoumarol, a specific inhibitor of DT-diaphorase. These results indicate that both DT-diaphorase and glutathione-S-transferase may be involved in the metabolism of daunorubicin.
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PMID:Enzyme induction by daunorubicin in neonatal heart cells in culture. 618 54

Daunomycin-induced cardiotoxicity has been regarded to be the result of oxygen-mediated lipid peroxidation of cell membranes. The aim of the present work was to evaluate the extent of lipid peroxidation in rat heart after administration of this anticancer drug and, further, to examine possible activation of some endogenous antioxidant defense systems. Myocardial tissue from both control and drug-treated rats was tested for lipid peroxidation using a selective third-order derivative method that is based on the analysis of the free malondialdehyde produced. Determination of reduced/oxidized glutathione levels and measurement of the activity of DT-diaphorase, glutathione-S-transferase, glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase were also carried out using literature methods. Significant increase of malondialdehyde content, and DT-diaphorase and glutathione-S-transferase activities were found in myocardial tissue from daunomycin-treated rats. On the other hand, reduced and oxidized glutathione levels were significantly decreased while the activity of glutathione reductase, glucose-6-phosphate dehydrogenase and NADPH-cytochrome P-450 reductase remained unchanged after daunomycin administration. The results of the present study give further evidence that daunomycin can induce lipid peroxidation in heart. However, additional experimentation is needed in order to delineate the molecular details of this process as well as of the mechanisms evolved to limit it.
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PMID:Lipid peroxidation of rat myocardial tissue following daunomycin administration. 962 May 40