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.