Adriamycin-induced oxidation of myoglobin.
Numerous mechanisms have been invoked to explain the cardiotoxicity of Adriamycin, most of which share a requirement for iron. Adriamycin is chemically reactive with iron loosely associated with subcellular membranes as well as with ferritin and the heme iron of hemoglobin. The present investigation examined whether Adriamycin also reacts with myoglobin, an abundant source of iron in cardiac muscle. Adriamycin caused a 4-fold stimulation of the autoxidation of oxymyoglobin to metmyoglobin. Hydrogen peroxide is an obligatory intermediate as catalase completely inhibited the reaction. Superoxide dismutase, however, was without effect. This interaction of Adriamycin with myoglobin may impose significant restrictions on oxygen storage and delivery in vivo. In light of the abundance of myoglobin and the deficiency of catalase in the heart, this interaction with myoglobin may be an important determinant of the cardioselective toxicity of Adriamycin.
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Department of Pharmacology, School of Medicine, University of Minnesota, Duluth 55812.
Wallace
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D000693:Anaerobiosis; D000818:Animals; D002374:Catalase / Q000378:metabolism / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology* / Q000633:toxicity; D006321:Heart / Q000187:drug effects; D006736:Horses; D007700:Kinetics; D008786:Metmyoglobin / Q000378:metabolism; D009132:Muscles / Q000378:metabolism; D009211:Myoglobin / Q000302:isolation & purification / Q000378:metabolism*; D010084:Oxidation-Reduction; D013482:Superoxide Dismutase / Q000378:metabolism / Q000494:pharmacology; D013997:Time Factors; D019820:Xanthine; D014969:Xanthine Oxidase / Q000378:metabolism; D014970:Xanthines / Q000378:metabolism
D009211:Myoglobin; D014970:Xanthines; C017595:oxymyoglobin; D008786:Metmyoglobin; D019820:Xanthine; D004317:Doxorubicin; D002374:Catalase; D013482:Superoxide Dismutase; D014969:Xanthine Oxidase