Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants

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 diff...

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Main Authors: J Fruebis, D A Bird, J Pattison, W Palinski
Format: Article
Language:English
Published: Elsevier 1997-12-01
Series:Journal of Lipid Research
Online Access:http://www.sciencedirect.com/science/article/pii/S0022227520300304
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author J Fruebis
D A Bird
J Pattison
W Palinski
author_facet J Fruebis
D A Bird
J Pattison
W Palinski
author_sort J Fruebis
collection DOAJ
description 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.
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spelling doaj.art-7e839e606dd84e5eaf1c86ba12f599da2022-12-21T17:15:40ZengElsevierJournal of Lipid Research0022-22751997-12-01381224552464Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidantsJ Fruebis0D A Bird1J Pattison2W Palinski3Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.Department of Medicine, University of California, San Diego, La Jolla 92093-0682, USA.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.http://www.sciencedirect.com/science/article/pii/S0022227520300304
spellingShingle J Fruebis
D A Bird
J Pattison
W Palinski
Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
Journal of Lipid Research
title Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
title_full Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
title_fullStr Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
title_full_unstemmed Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
title_short Extent of antioxidant protection of plasma LDL is not a predictor of the antiatherogenic effect of antioxidants
title_sort extent of antioxidant protection of plasma ldl is not a predictor of the antiatherogenic effect of antioxidants
url http://www.sciencedirect.com/science/article/pii/S0022227520300304
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