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 < 0.005), whereas the
antioxidant combination failed to reduce lesion formation. Thus, the lag-time is clearly not correlated with the antiatherogenic efficacy of different
antioxidants. However, a weak correlation was found within the group treated with
probucol only. Our results suggest that the degree of
antioxidant protection of plasma
LDL may not be a good
indicator of the atherogenic risk, in general, and that
probucol reduces
atherogenesis by mechanisms not shared by all
antioxidants.