Microsomal lipid peroxidation induced by adriamycin, epirubicin, daunorubicin and mitoxantrone: a comparative study.
Rat-liver microsomes and NADPH could reduce Adriamycin, epirubicin and daunorubicin to their free radical forms, which enhanced peroxidation of microsomal lipids less than 2-fold in air but 3- to 5-fold at a pO2 of 4 mmHg. Mitoxantrone was not reduced by microsomes and had no effect on microsomal peroxidation. Daunorubicin caused more lipid peroxidation than similar concentrations of either Adriamycin or epirubicin, which were equally efficient. In each case peroxidation was iron-dependent and could be catalysed by ferritin. The antioxidants beta-carotene and alpha-tocopherol inhibited lipid peroxidation at low or high pO2. The dose-for-dose difference in the cardiotoxicity of epirubicin compared with Adriamycin is not explained by its effect on microsomal lipid peroxidation. However, the lower incidence of cardiotoxicity with mitoxantrone may be a consequence of its inability to form free radical species and promote lipid peroxidation.
Vile
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GF
Department of Pathology, Christchurch School of Medicine, Christchurch Hospital, New Zealand.
Winterbourn
C C
CC
D000818:Animals; D002338:Carotenoids / Q000494:pharmacology; D002384:Catalysis; D003574:Cytochrome c Group / Q000378:metabolism; D003630:Daunorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D004317:Doxorubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015251:Epirubicin / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D005293:Ferritins / Q000494:pharmacology; D007501:Iron / Q000494:pharmacology; D015227:Lipid Peroxidation / Q000187:drug effects*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D008942:Mitoxantrone / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010100:Oxygen / Q000494:pharmacology; D010313:Partial Pressure; D051381:Rats; D011919:Rats, Inbred Strains; D014810:Vitamin E / Q000494:pharmacology; D019207:beta Carotene
D003574:Cytochrome c Group; D019207:beta Carotene; D014810:Vitamin E; D002338:Carotenoids; D015251:Epirubicin; D004317:Doxorubicin; D005293:Ferritins; D008942:Mitoxantrone; D007501:Iron; D010100:Oxygen; D003630:Daunorubicin