General oxidative stress during doxorubicin-induced cardiotoxicity in rats: Absence of cardioprotection and low antioxidant efficiency of alpha-lipoic acid

To evaluate the effects of alpha-lipoic acid (AL) in a model of doxorubicin (DOX)-induced cardiotoxicity, male Wistar rats were treated with DOX (1 mg/kg/d; 10 d) in combination or not with AL (50 mg/kg/d; 15 d). Plasma oxidative stress was determined by hydroperoxides (ROOH) and the ascorbyl radical/ascorbate ratio. One and two months later, the functional parameters of the hearts were determined in vivo by catheterization and cardiac oxidative stress was assessed by malonedialdehyde (MDA) and O-2(center dot-) (dihydroethidium fluorescence) content in tissue. After two months, body weight was higher in the DOX-AL group than in DOX (+16%), but this was due to ascites. Histological liver alterations were observed in both the DOX and DOX-AL groups. Plasma ROOH concentrations decreased after 10 days of AL treatment, but were greater in both the DOX and DOX-AL groups. After two months, a decrease in the cardiac contractility index (-27% and -29%, respectively) and cardiac hypertrophy were observed in DOX and DOX-AL These dysfunctions were associated with I) a reduction in plasma ascorbate levels and an increase in the ascorbyl/ascorbate ratio and 2) an increase MDA and O-2(center dot-) content in cardiac tissue. In conclusion, a cumulative dose of 10 mg/kg doxorubicin induced functional alterations in the heart associated with plasma and cardiac oxidative stress. The co-administration of the antioxidant compound AL had no beneficial effects in this situation. (C) 2011 Published by Elsevier Masson SAS.