Effects of probucol on impaired cardiac performance and lipid metabolism in streptozotocin-induced diabetic rats.
Plasma lipids and cardiac performance were studied in diabetic rats treated with probucol. Male Wistar rats were rendered diabetic with a single intraperitoneal injection of streptozotocin (STZ, 75 mg/kg). Nondiabetic control rats received the vehicle alone. Two weeks after STZ or vehicle injection, control and diabetic rats were randomly assigned to probucol-treated or untreated groups. The rats in the two probucol-treated groups (control- and diabetic-probucol groups) were fed a diet containing 1% probucol (w/w) for 4 weeks. Blood was drawn, and then cardiac performance was assessed by the isolated perfused working heart technique. Probucol treatment had no effect on the cardiac performance of the nondiabetic control rats. The peak left ventricular developed pressure and maximum rate of change in left ventricular pressure during systole were significantly greater in the probucol-treated diabetic rats than in the untreated diabetic rats (p less than 0.05), although cardiac performance did not improve to the level in the nondiabetic rats. Plasma cholesterol, free fatty acid, and phospholipid were significantly elevated in the untreated diabetic rats, and probucol treatment decreased significantly the plasma cholesterol and free fatty acid concentrations (p less than 0.05). These data suggest that probucol treatment improves plasma lipids and cardiac performance in rats with experimental diabetes and may prevent diabetic cardiomyopathy.
Tada
H
H
Third Department of Internal Medicine, Fukui Medical School, Japan.
Oida
K
K
Kutsumi
Y
Y
Shimada
Y
Y
Nakai
T
T
Miyabo
S
S
D000818:Animals; D001693:Biological Transport, Active; D001786:Blood Glucose / Q000032:analysis; D001835:Body Weight / Q000187:drug effects; D002118:Calcium / Q000378:metabolism; D002302:Cardiac Output / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000378:metabolism / Q000503:physiopathology*; D007328:Insulin / Q000097:blood; D008055:Lipids / Q000097:blood*; D008297:Male; D015425:Myocardial Reperfusion; D011341:Probucol / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D016277:Ventricular Function, Left / Q000187:drug effects
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D011341:Probucol; D002118:Calcium