Toxic effects of daunorubicin on isolated and cultured heart cells from neonatal rats

dc.contributor.authorGalaris, D.en
dc.contributor.authorGeorgellis, A.en
dc.contributor.authorRydstrom, J.en
dc.date.accessioned2015-11-24T19:12:44Z
dc.date.available2015-11-24T19:12:44Z
dc.identifier.issn0006-2952-
dc.identifier.urihttps://olympias.lib.uoi.gr/jspui/handle/123456789/21109
dc.rightsDefault Licence-
dc.subjectAnimalsen
dc.subjectAnimals, Newbornen
dc.subjectCells, Cultureden
dc.subjectDaunorubicin/metabolism/*toxicityen
dc.subjectGlutathione/secretionen
dc.subjectHeart/*drug effectsen
dc.subjectL-Lactate Dehydrogenase/secretionen
dc.subjectLipid Peroxides/metabolismen
dc.subjectMyocardium/metabolismen
dc.subjectQuinone Reductases/biosynthesisen
dc.subjectRatsen
dc.titleToxic effects of daunorubicin on isolated and cultured heart cells from neonatal ratsen
heal.abstractVarious 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.en
heal.accesscampus-
heal.fullTextAvailabilityTRUE-
heal.identifier.secondaryhttp://www.ncbi.nlm.nih.gov/pubmed/3986001-
heal.identifier.secondaryhttp://www.sciencedirect.com/science/article/pii/000629528590601X-
heal.journalNameBiochem Pharmacolen
heal.journalTypepeer-reviewed-
heal.languageen-
heal.publicationDate1985-
heal.recordProviderΠανεπιστήμιο Ιωαννίνων. Σχολή Επιστημών Υγείας. Τμήμα Ιατρικήςel
heal.typejournalArticle-
heal.type.elΆρθρο Περιοδικούel
heal.type.enJournal articleen

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