Stimulation of myoglobin-dependent lipid peroxidation by adriamycin.
The objective of this investigation was to determine whether myoglobin can serve as a physiological source of iron in the catalysis of Adriamycin-stimulated lipid peroxidation. In vitro peroxidation of arachidonic acid was stimulated 2-fold by 50 microM Adriamycin, the extent of lipid peroxidation being dependent on the duration of incubation and the concentrations of both Adriamycin and myoglobin. Differential inhibition studies suggest that hydroxyl radicals are involved in this reaction; however, superoxide and hydrogen peroxide were not implicated. The results demonstrate a potentially important stimulation by Adriamycin of myoglobin-dependent membrane-lipid peroxidation. In light of the abundance of myoglobin and the deficiency of oxygen radical detoxifying enzymes in the heart, this interaction may be a significant 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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D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D017665:Hydroxyl Radical / Q000378:metabolism; D007700:Kinetics; D008027:Light; D015227:Lipid Peroxidation / Q000187:drug effects*; D008786:Metmyoglobin / Q000187:drug effects / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009211:Myoglobin / Q000187:drug effects / Q000378:metabolism*; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis / Q000378:metabolism; D013997:Time Factors
D009211:Myoglobin; D017392:Thiobarbituric Acid Reactive Substances; C017595:oxymyoglobin; D008786:Metmyoglobin; D016718:Arachidonic Acid; D017665:Hydroxyl Radical; D004317:Doxorubicin