The effect of vitamin E, probucol, and lovastatin on oxidative status and aortic fatty lesions in hyperlipidemic-diabetic hamsters

Diabetes mellitus is associated with an increased risk of premature atheros clerosis, which may be due in part to an increased rate of low density lipo protein (LDL) oxidation. Previous studies have shown that vitamin E, probuc ol, and lovastatin can reduce the oxidative susceptibility of LDL in normog lycemic animal models; however, few studies have investigated this in conju nction with aortic fatty streak lesion formation in diabetic hyperlipidemic models. Forty-eight Syrian hamsters were made diabetic by intraperitoneal injection of low dose streptozotocin. Diabetic animals (12 animals/groups) received a high saturated fat and cholesterol diet for 12.5 weeks. At 2.5 w eek of dietary treatments, the diet was supplemented with either: (1) 500 I U/day vitamin E (D + E); (2) 1% probucol w/w of the diet (D + P); (3) 25 mg /kg lovastatin (D + L); or (4) diabetic control (D). An age-matched group o f hamsters (n = 6) receiving the same diet but not made diabetic (ND) was u sed as control. At the end of the study, aortic arch foam cell-rich fatty s treak lesion, plasma glucose, total cholesterol (TC), high density lipoprot ein cholesterol (HDL-C), non-HDL-C, triglycerides (TG), phospholipids, cc-t ocopherol, plasma lipid peroxide and the susceptibility of LDL to copper-ca talyzed oxidation were determined. Diabetes increased plasma glucose, and w hen combined with an atherogenic diet resulted in a further increase of pla sma lipids. Vitamin E, probucol, and lovastatin significantly reduced plasm a TG in the diabetic hamsters fed the atherogenic diet. Vitamin E treatment increased TC, probucol reduced HDL-C without affecting TC; whereas lovasta tin reduced TC and selectively decreased non-HDL-C, and significantly reduc ed fatty streak lesion formation in the aortic arch. While vitamin E and pr obucol were effective in reducing several indices of oxidative stress inclu ding plasma lipid peroxides, cholesterol oxidation products and in vitro LD L oxidation, they had no effect on fatty streak lesion formation. Our resul ts indicate that the LDL in diabetic animals is more susceptible to oxidati on than in non-diabetic hamsters and that not only vitamin E and probucol b ut also lovastatin provide antioxidant protection. It appears that in this combined model of diabetes and hypercholesterolemia, progression of fatty s treak lesion formation is mainly associated with changes in TC and non-HDL- C as affected by lovastatin, and is less dependent on the extent of LDL oxi dation, changes in plasma TG level and oxidative stress status. (C) 2000 El sevier Science Ireland Ltd. All rights reserved.