EFFECT OF CHOLESTEROL-RICH DIETS WITH AND WITHOUT ADDED VITAMIN-E ANDVITAMIN-C ON THE SEVERITY OF ATHEROSCLEROSIS IN RABBITS

Oxysterols as oxidation products of cholesterol are considered an athe rogenic factor in the development of atherosclerosis in the arteries o f cholesterol-fed rabbits. We compared the atherogenic effects of diet s enriched either with 0.5% oxidized cholesterol (OC; characterized by high amounts of oxysterols) or with pure cholesterol (PC). The effect s of antioxidant vitamins E and C added to the PC diet were also evalu ated in view of their antioxidative properties for lipoproteins and ch olesterol and how this could affect the severity of atherosclerosis. F our groups of rabbits were fed the following for 11 wk: 1) a nonpurifi ed stock diet, 2) this stock diet plus 0.5% OC, 3) the stock diet plus 0.5% PC, and 4) the stock diet plus 0.5% PC and 1000 mg vitamin E and 500 mg vitamin C/kg diet (PC + antioxidants). The OC and PC diets wer e equally hyperlipidemic and hypercholesterolemic. The severity of ath erosclerotic lesions was highest with the OC diet and lowest with the PC + antioxidants diet. The plasma oxysterol concentration was proport ional to the severity of atherosclerosis in all three groups of choles terol-fed rabbits. beta-Very-low-density-lipoprotein modification was minimized by vitamins E and C as indicated by its polyacrylamide gel e lectrophoretic pattern and its increased binding to the rabbit liver m embrane in vitro. This study indicated that OC and PC were equally ath erogenic but that the addition of antioxidants to the PC diet signific antly reduced its severity, even when hypercholesterolemia persisted. This indicated that atherogenesis can result from an excessive accumul ation of oxidation products of cholesterol in the plasma.