Comparative cardiac oxygen radical metabolism by anthracycline antibiotics, mitoxantrone, bisantrene, 4'-(9-acridinylamino)-methanesulfon-m-anisidide, and neocarzinostatin.
This study examined the effects of various anthracycline antibiotics and mitoxantrone, bisantrene, 4'-(9-acridinylamino)-methanesulfon-m-anisidide (m-AMSA), and neocarzinostatin on oxygen radical formation by cardiac sarcoplasmic reticulum and submitochondrial particles. Doxorubicin, daunorubicin, rubidazone, and aclacinomycin A stimulated superoxide production by both heart fractions in a dose-dependent fashion that appeared to follow saturation kinetics. The anthracycline drugs also significantly increased hydrogen peroxide production by heart sarcosomes and submitochondrial particles. On the other hand, mitoxantrone, bisantrene, m-AMSA, and neocarzinostatin did not significantly enhance cardiac reactive oxygen metabolism. Thus, it is unlikely that the mechanism of the cardiac toxicity produced by mitoxantrone and m-AMSA in patients previously treated with anthracycline drugs can be directly related to oxidation-reduction cycling catalyzed by cardiac flavin dehydrogenases.
D000609:Aminoacridines / Q000494:pharmacology*; D000677:Amsacrine; D000818:Animals; D000873:Anthracenes / Q000494:pharmacology; D000880:Anthraquinones / Q000494:pharmacology*; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D008297:Male; D008929:Mitochondria, Heart / Q000378:metabolism; D008942:Mitoxantrone; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012519:Sarcoplasmic Reticulum / Q000378:metabolism; D013367:Submitochondrial Particles / Q000378:metabolism; D013481:Superoxides / Q000378:metabolism*; D009353:Zinostatin / Q000494:pharmacology*
D000609:Aminoacridines; D000873:Anthracenes; D000880:Anthraquinones; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D000677:Amsacrine; D013481:Superoxides; C031404:bisantrene; D009353:Zinostatin; D008942:Mitoxantrone