PROBUCOL IMPROVES ANTIOXIDANT ACTIVITY AND MODULATES DEVELOPMENT OF DIABETIC CARDIOMYOPATHY

To examine the role of free radicals in diabetic cardiomyopathy, myoca rdial antioxidants as well as lipid peroxide content were examined in rats made diabetic with a single injection of streptozotocin (65 mg/kg IV). At 4 wk, the left ventricular peak systolic (LVSP) as well as ao rtic pressures were depressed in the diabetic group. Hearts from diabe tic animals showed about a 100% increase in thiobarbituric acid reacti ve substances (TEARS), indicating increased lipid peroxidation. This w as accompanied by about a 50% decrease in superoxide dismutase (SOD) a nd 60% decrease in glutathione peroxidase (GSHPx) enzyme activities. C atalase activity in these hearts showed a small but significant increa se. Treatment with probucol (10 mg/kg i.p., on alternate days), a know n lipid-lowering drug with strong antioxidant properties, was initiate d 1 d after the induction of diabetes and was continued for 4 wk. In p robucol-treated diabetic animals, LVSP was not different from controls . Probucol treatment caused a small but significant improvement in ser um insulin and decrease in glucose levels as well as increased myocard ial SOD, GSHPx, and catalase activities with a concomitant decrease in TEARS in the diabetic animals. These data provide evidence that diabe tic cardiomyopathy is associated with an antioxidant deficit, and a be tter cardiac function due to treatment with probucol may be related to the improved insulin levels as well as maintenance of the antioxidant status of the heart.