Protective effects of carvedilol against doxorubicin-induced cardiomyopathy in rats

Abstract

Carvedilol (CAR) is a vasodilating β-blocker which also has antioxidant properties. CAR produces dose-related reduction in mortality in patients with congestive heart failure. In the present study, we tested the hypothesis that CAR protects against doxorubicin (DOX)-induced cardiomyopathy in rats. Sprague-Dawley rats were treated with DOX, CAR, CAR+DOX, or atenolol (ATN)+DOX. DOX (cumulative dose, 15 mg kg ) was administered intraperitoneally, and CAR (30 mg kg daily) or ATN (150 mg kg daily) was administered orally. Three weeks after the completion of these treatments, cardiac performance and myocardial lipid peroxidation were assessed. Mortality was observed in the DOX (25%) and ATN+DOX (12.5%) groups. Compared with control rats, DOX significantly decreased systolic blood pressure (104 ± 4 vs. 120 ± 4 mmHg, P < 0.05) and left ventricular fractional shortening (38.8 ± 3.1 vs. 55.4 ± 1.3%, P < 0.01), and resulted in a significant accumulation of ascites (14.4 ± 4.9 vs. 0 ml, P < 0.01). CAR significantly prevented the cardiomyopathic changes caused by DOX, while ATN did not. The myocardial thiobarbituric acid reactive substances (TBARS) content was significantly higher in DOX-treated rats than in control rats (80.4 ± 7.1 vs. 51.5 ± 1.2 nmol g heart, p < 0.01). CAR prevented the increase in TBARS content (48.8 ± 3.0 nmol g heart, P < 0.01 vs. DOX group), whereas ATN had no significant effect (74.3 ± 5.2 nmnol g heart). CAR also significantly prevented the increase in both myocardial and plasma cholesterol concentrations caused by DOX. These data indicate that CAR protects against DOX-induced cardiomyopathy and that this effect may be attributed to the antioxidant and lipid-lowering properties of CAR, not to its β-blocking property.