出版社:American Society for Biochemistry and Molecular Biology
摘要:Oxidation of LDL plays all important role in atherogenesis. The lag-time in the formation of conjugated dienes provides a sensitive measure of the resistance of plasma LDL to oxidation and is widely assumed to be an indicator of atherogenic risk. To test this assumption, we investigated whether different antioxidants yielding similar lag-times result in similar reduction of atherosclerosis. A 6-months intervention study was carried out in three groups of 10 LDL receptor-deficient rabbits each. Because previous studies indicated that antioxidants that reduce atherosclerosis resulted in very long lag-times, the first group was treated with an antioxidant combination containing 1,000 IU vitamin E, 0.05% probucol analogue (BM15.0639), and 0.025% probucol. The lag-times achieved throughout the intervention period by this combination (952 +/- 39 min) were matched in a second group (829 +/- 46 min) treated with a variable dose of probucol (0.0575-0.11%, average 0.091%). A third, untreated group served as a control. Plasma cholesterol levels of all groups were matched. Even though both treatments yielded similar antioxidant protection of plasma LDL, 0.091% probucol reduced aortic atherosclerosis by 51.7% compared to the untreated group (P