Antioxidants protect against reactive oxygen species associated with adriamycin-treated cardiomyocytes

Adriamycin (ADM) is a broad-spectrum antineoplastic antibiotic used to trea t cancer patients. However, the usefulness of this drug is presently limite d by the development of a dose-dependent cardiotoxicity. A current hypothes is for the ADM-induced cardiotoxicity is the production of reactive oxygen radicals by the drug. We utilized the fluorescent indicator 2',7'-dichlorod ihydrofluorescein diacetate (DCFH/DA), in which fluorescence appears if rea ctive oxygen species (ROS) are present, to investigate the ability of ADM t o generate reactive oxygen species and the potential protective effect of a ntioxidants in a cultured cardiomyocyte model. All three of the antioxidant s (alpha-phenyl-tert-butyl nitrone (PBN), trolox, and 5-aminosalicyclic aci d (5-ASA)) tested in our ADM-treated myocytes provided protection against t he oxidative stress induced by the drug. These findings suggest that antiox idants modulate ADM-induced oxidative stress, and they are discussed in ter ms of a possible therapeutic strategy in the prevention of cardiotoxicity r esulting from ADM administration. (C) 1999 Published by Elsevier Science Lt d. All rights reserved.