Effects of probucol on changes of antioxidant enzymes in adriamycin-induced cardiomyopathy in rats

Objective: The clinical usefulness of doxorubicin (adriamycin, ADR) is rest ricted by the risk of developing congestive heart failure. Probucol has bee n reported to completely prevent ADR cardiomyopathy without interfering wit h its antitumor effects. The current study investigated the effects of ADR and probucol on antioxidant enzyme gene expression during adriamycin-induce d cardiomyopathy in a rat model. Methods: The mRNA abundance by Northern an d immunoreactive protein levels by Western blotting of myocardial antioxida nt enzymes, glutathione peroxidase (GSHPx), manganese superoxide dismutase (MnSOD) and catalase (CAT) were examined in relation to the enzyme activiti es in hemodynamically assessed control and treated animals. Results: At 3 w eeks post-treatment duration, ADR caused heart failure which was prevented by probucol. MnSOD mRNA abundance as well as protein levels were depressed by ADR treatment by 45% and 20%, respectively, and this change was prevente d by probucol. However, the mRNA and protein levels of GSHPx and CAT were n ot significantly changed by ADR or probucol. ADR had no effect on SOD activ ity but this enzyme activity was increased by probucol and probucol plus AD R. GSHPx enzyme activity was decreased and oxidative stress as indicated by TEARS was increased by ADR and these changes were also modulated by probuc ol. Conclusion: An increase in oxidative stress, GSHPx inactivation and MnS OD downregulation during ADR cardiomyopathy were prevented by probucol trea tment. (C) 2000 Elsevier Science B.V. All rights reserved.