Probucol improves antioxidant activity and modulates development of diabetic cardiomyopathy.
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.
Kaul
N
N
Division of Cardiovascular Sciences, St. Boniface General Hospital Research Centre, Winnipeg, Canada.
Siveski-Iliskovic
N
N
Thomas
T P
TP
Hill
M
M
Khaper
N
N
Singal
P K
PK
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
D000924:Anticholesteremic Agents; D000975:Antioxidants; D005609:Free Radicals; D017392:Thiobarbituric Acid Reactive Substances; D002374:Catalase; D005979:Glutathione Peroxidase; D013482:Superoxide Dismutase; D011341:Probucol