PROBUCOL TREATMENT REVERSES ANTIOXIDANT AND FUNCTIONAL DEFICIT IN DIABETIC CARDIOMYOPATHY

Earlier we reported that probucol treatment subsequent to the inductio n of diabetes can prevent diabetes-associated changes in myocardial an tioxidants as well as function at 8 weeks. In this study, we examined the efficacy of probucol in the reversal of diabetes induced myocardia l changes. Rats were made diabetic with a single injection of streptoz otocin (65 mg/kg, i.v.). After 4 weeks of induction of diabetes, a gro up of animals was treated on alternate days with probucol (10 mg/kg i. p.), a known lipid lowering agent with antioxidant properties. At 8 we eks, there was a significant drop in the left ventricle (LVSP) and aor tic systolic pressures (ASP) in the diabetic group. Hearts from these animals showed an increase in the thiobarbituric acid reacting substan ces (TBARS), indicating increased lipid peroxidation. This was accompa nied by a decrease in the myocardial antioxidant enzymes activities, s uperoxide dismutase (SOD) and glutathione peroxidase (GSHPx). Myocardi al catalase activity in the diabetic group was higher. In the diabetic + probucol group both LVSP and ASP showed significant recovery. This was also accompanied by an improvement in SOD and GSHPx activities and there was further increase in the catalase activity. Levels of the TB ARS were decreased in this group. These data provide evidence that dia betic cardiomyopathy is associated with an antioxidant deficit which c an be reversed with probucol treatment. Improved cardiac function with probucol may be due to the recovery of antioxidants in the heart.