title: Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy.
abstract: To examine the role of free radicals in diabetic cardiomyopathy, myocardial antioxidants as well as lipid peroxide content were examined in rats made diabetic with a single injection of streptozotocin (65 mg/kg i.v). At 4 wk, the left ventricular peak systolic (LVSP) as well as aortic pressures were depressed in the diabetic group. Hearts from diabetic animals showed about a 100% increase in thiobarbituric acid reactive substances (TBARS), indicating increased lipid peroxidation. This was accompanied by about a 50% decrease in superoxide dismutase (SOD) and 60% decrease in glutathione peroxidase (GSHPx) enzyme activities. Catalase activity in these hearts showed a small but significant increase. Treatment with probucol (10 mg/kg i.p., on alternate days), a known lipid-lowering drug with strong antioxidant properties, was initiated 1 d after the induction of diabetes and was continued for 4 wk. In probucol-treated diabetic animals, LVSP was not different from controls. Probucol treatment caused a small but significant improvement in serum insulin and decrease in glucose levels as well as increased myocardial SOD, GSHPx, and catalase activities with a concomitant decrease in TBARS in the diabetic animals. These data provide evidence that diabetic cardiomyopathy is associated with an antioxidant deficit, and a better 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.
authors: Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
authors: N
authors: N
authors: Kaul
authors: N
authors: N
authors: Siveski-Iliskovic
authors: T P
authors: TP
authors: Thomas
authors: M
authors: M
authors: Hill
authors: N
authors: N
authors: Khaper
authors: P K
authors: PK
authors: Singal
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000627:therapeutic use*; D000975:Antioxidants; D009202:Cardiomyopathies / Q000209:etiology* / Q000517:prevention & control*; D002374:Catalase / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000150:complications*; D005609:Free Radicals; D005979:Glutathione Peroxidase / Q000378:metabolism; D015227:Lipid Peroxidation; D008297:Male; D009206:Myocardium / Q000378:metabolism; D011341:Probucol / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
chemical_list: D000924:Anticholesteremic Agents; D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011341:Probucol