The effect of pharmacological doses of different antioxidants on oxidationparameters and atherogenesis in hyperlipidaemic rabbits

The oxidation hypothesis of atherosclerosis implies that antioxidants are a ble to inhibit lipoprotein oxidation in the arterial wall and thereby retar d atherogenesis. Since most of the animal studies performed have used very, high doses of antioxidants, it is to date unknown whether antioxidants are effective antiatherosclerotic agents when given in pharmacological doses. Here we addressed this question using homozygous Watanabe heritable hyperli pidaemic (WHHL) rabbits as an animal model of atherosclerosis. The rabbits were divided into four groups, each consisting of ten animals. They receive d either a standard diet or a diet containing 4.3 mg ubiquinone-10, or 4.3 mg vitamin E or 15 mg probucol/kg body weight daily. After 12 months, the e xtent of aortic atherosclerosis was assessed as the intima thickness, media thickness and intima-to-media ratio in 14 cross sections equally distribut ed over the whole aorta. To evaluate the antioxidant effects of the diet, l ipophilic and hydrophilic antioxidants, lipids, fatty acids and plasma oxid izability were measured after 0, 3 and 6 months of Feeding. We found that s upplementation with probucol significantly decreased aortic intima-to-media ratio compared to controls. The antiatherosclerotic action of probucol was accompanied by its beneficial action on plasma oxidizability and some plas ma antioxidants. No decrease in aortic atherosclerosis was measured in ubiq uinone-10- and vitamin E-supplemented rabbits, despite the fact that both a ntioxidants decreased plasma oxidizability and ubiquinone-10 increased the plasma levels of antioxidants. Taken together, these data suggest that phar macological doses of probucol retard atherogenesis in WHHL rabbits by an an tioxidant mechanism, while ubiquinone-10 and vitamin E at these dosages are ineffective in this highly hyperlipidaemic model. The measurement of some oxidation-related parameters in plasma, such as lipophilic antioxidants, po lyunsaturated fatty acids and lipoprotein oxidizability. may be useful in a ssessing the risk of atherogenesis in humans. (C) 2001 Elsevier Science ire land Ltd. All rights reserved.