COMPARATIVE-STUDY ON THE EFFECT OF LOW-DOSE VITAMIN-E AND PROBUCOL ONTHE SUSCEPTIBILITY OF LDL TO OXIDATION AND THE PROGRESSION OF ATHEROSCLEROSIS IN WATANABE HERITABLE HYPERLIPIDEMIC RABBITS

The diet of Watanabe heritable hyperlipidemic (WHHL) rabbits was suppl emented with a low dose (0.025% [wt/wt]) of the antioxidant vitamin E or probucol. The effect of 6 months of treatment on the susceptibility of low-density lipoproteins (LDLs) to oxidative modification and on e stablished atherosclerotic lesions was studied. Vitamin E administrati on had no effect on plasma lipid levels; probucol supplementation decr eased plasma total cholesterol. Vitamin E levels in plasma and LDL inc reased threefold in the course of treatment with this antioxidant. Six months of treatment with vitamin E and probucol increased the lag tim e of conjugated-diene formation of LDL subjected to in vitro oxidation by 54% (P<.001) and 51% (P=.019), respectively. In this LDL-oxidizabi lity assay, only vitamin E reduced the maximal rate of conjugated-dien e production (-24%, P<.001). Neither vitamin E treatment nor probucol therapy reduced the amount of thiobarbituric acid-reactive substances in plasma. Vitamin E treatment reduced the specific LDL apolipoprotein B-100 fluorescence (-10%, P=.035) compared with controls. Probucol wa s without effect on this index of in vivo LDL oxidation. At the end of the 6-month study, the mean+/-SD percentage area of aorta covered wit h plaques was 58.7+/-10.1% in control animals, 62.7+/-12.0% in the pro bucol-treated animals, and 48.9+/-13.8% in the animals treated with vi tamin E; these differences were not significant. This study demonstrat es that at this low dosage, vitamin E is a more effective antioxidant than probucol.