It has been proposed that the cardiotoxicity of doxorubicin (DOX) is mediated via oxidative mechanisms. Experiments examined this hypothesis by determining if effects of DOX-treatment on contractility are paralleled by changes in glutathione levels or lipid peroxidation (as monitored via levels of malonyldialdehyde, MDA). Rats were injected with a single dose of 4, 6 or 8 mg/kg DOX (or solvent) 3 or S weeks before tissue isolation. Contractility was monitored in trial (AM) and papillary (PM) muscle that was bathed in Krebs-Henseleit solution (30°C). Glutathione and MDA were monitored in ventricular tissue using standard assays. ' DOXtreatment elicited decreases in rest-potentiated developed tension and the isoproterenol-induced positive inotropic effect in both AM and PM. The force-frequency relationship showed a DOX-associated decrease in basal developed tension in AM at frequencies between 0.1 and 0.5 Hz; however, PM showed no differences in basal developed tension at any frequency from 0.1 to 4.S Hz. Glutathione levels were decreased, while MDA was increased in ventricular myocardium by DOX-treatment. There were no differences in tissues isolated 3 or 5 weeks after injection of DOX. These data support the hypothesis that the cardiomyopathy elicited by DOX is mediated, at least in part, by oxidative damage.
|Published - 1996
ASJC Scopus subject areas
- Agricultural and Biological Sciences (miscellaneous)
- General Biochemistry, Genetics and Molecular Biology
- Cell Biology