Mechanisms of beneficial effects of probucol in adriamycin cardiomyopathy

Probucol, a lipid-lowering drug, has been shown to offer protection against adriamycin-induced cardiomyopathy. In order to define the mechanism of thi s protection, we examined changes in antioxidants and lipid peroxidation in hearts as well as lipids in hearts and plasma from rats treated with eithe r adriamycin or adriamycin and probucol with appropriate controls. Any pote ntial free radical quenching as well as growth inhibitory effects of probuc ol were also examined using Chinese hamster ovary (CHO) cells in culture. I n animal model, adriamycin caused a significant depression in glutathione p eroxidase and increased plasma and cardiac lipids as well as lipid peroxida tion. Probucol treatment modulated adriamycin-induced cardiomyopathic chang es and increased glutathione peroxidase and superoxide dismutase activities . In the presence of adriamycin under hypoxic conditions, formation of adri amycin semiquinone radical was detected by ESR. The cell growth in these cu ltures was also inhibited by adriamycin in a dose-dependent manner. Probuco l had no effect on adriamycin-induced growth inhibition as well as formatio n of semiquinone radicals. It is proposed that probucol protection against adriamycin cardiomyopathy is mediated by increased antioxidants and lipid-l owering without any effect on free radical production.