zinostatin and bisantrene

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.

Topics: Aminoacridines; Amsacrine; Animals; Anthracenes; Anthraquinones; Antibiotics, Antineoplastic; Antineoplastic Agents; Male; Mitochondria, Heart; Mitoxantrone; Myocardium; Rats; Rats, Inbred Strains; Sarcoplasmic Reticulum; Submitochondrial Particles; Superoxides; Zinostatin