Adriamycin-induced early changes in myocardial antioxidant enzymes and their modulation by probucol

Background-The clinical usefulness of adriamycin is restricted by the devel opment of congestive heart failure. It has been suggested that probucol, a strong antioxidant, completely prevents adriamycin-induced cardiomyopathy w ithout interfering with its antitumor properties. The present study investi gated the effects of adriamycin and probucol on myocardial antioxidant enzy me activities and immunoreactive protein levels in rats. Methods and Results-Activities and protein levels of glutathione peroxidase (GSHPx) were significantly decreased from 2 to 24 hours, and those of mang anese superoxide dismutase were decreased at 1 and 2 hours after adriamycin treatment. These changes were prevented by probucol. Catalase activity was increased from 2 to 24 hours after adriamycin treatment, but its protein l evels were not significantly changed. Copper zinc superoxide dismutase acti vity and protein level were not changed at any time. Myocardial lipid perox idation was found to be significantly higher at all time points, and this c hange was also prevented by probucol. Treatment with probucol alone increas ed GSHPx activity at 2 weeks, and in these hearts, lipid peroxidation was l ower than the control value. Within 24 hours, there was no mortality in any of the groups. Conclusions-It is suggested that an early and persistent decrease in GSHPx activity and protein may play an important role in the pathogenesis of adri amycin-induced cardiomyopathy, worsening heart failure and mortality.