OH.-generation by adriamycin semiquinone and H2O2; an explanation for the cardiotoxicity of anthracycline antibiotics.
Anthracycline-induced cardiomyopathy is still a matter of discussion. The many mechanisms proposed cannot explain a selective sensitivity of the heart to these antitumor drugs. The present paper provides experimental evidence which shows that heart tissue has special biochemical conditions which favour an anthracycline-catalysed electron shuttle to H2O2. This results in the generation of highly reactive OH.-radicals, instead of O-.2-radicals, which are expected to be formed in tissues also supplemented with anthracycline-activating microsomal enzyme systems.
D000818:Animals; D004317:Doxorubicin / Q000031:analogs & derivatives* / Q000378:metabolism / Q000633:toxicity*; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D006321:Heart / Q000187:drug effects*; D006861:Hydrogen Peroxide; D006878:Hydroxides; D017665:Hydroxyl Radical; D008297:Male; D008861:Microsomes / Q000378:metabolism; D008862:Microsomes, Liver / Q000378:metabolism; D008929:Mitochondria, Heart / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains
D005609:Free Radicals; D006878:Hydroxides; C024703:adriamycin semiquinone radicals; D017665:Hydroxyl Radical; D004317:Doxorubicin; D006861:Hydrogen Peroxide