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Research Communications |
Biochemistry Group, Heart Research Institute, Sydney, Australia; and
a Astra Hässle, Mölndal, S-43183, Sweden
Antioxidants can inhibit atherosclerosis
in animals, though it is not clear whether this is due to the
inhibition of aortic lipoprotein lipid (per)oxidation. Coantioxidants
inhibit radical-induced, tocopherol-mediated peroxidation of lipids in
lipoproteins through elimination of tocopheroxyl radical. Here we
tested the effect of the bisphenolic probucol metabolite and
coantioxidant H 212/43 on atherogenesis in apolipoprotein E and low
density lipoprotein (LDL) receptor gene double knockout
(apoE-/-;LDLr-/-) mice, and how this related to aortic lipid
(per)oxidation measured by specific HPLC analyses. Dietary
supplementation with H 212/43 resulted in circulating drug levels of
~200 µM, increased plasma total cholesterol slightly and decreased
plasma and aortic 
-tocopherol significantly relative to age-matched
control mice. Treatment with H 212/43 increased the antioxidant
capacity of plasma, as indicated by prolonged inhibition of peroxyl
radical-induced, ex vivo lipid peroxidation. Aortic tissue
from control apoE-/-;LDLr-/- mice contained lipid hydro(pero)xides
and substantial atherosclerotic lesions, both of which were decreased
strongly by supplementation of the animals with H 212/43. The results
show that a coantioxidant effectively inhibits in vivo
lipid peroxidation and atherosclerosis in apoE-/-;LDLr-/- mice,
consistent with though not proving a causal relationship between aortic
lipoprotein lipid oxidation and atherosclerosis in this model of the
disease.—Witting, P. K., Pettersson, K., Östlund-Lindqvist,
A.-M., Westerlund, C., Westin Eriksson, A., Stocker, R. Inhibition by a
coantioxidant of aortic lipoprotein lipid peroxidation and
atherosclerosis in apolipoprotein E and low density lipoprotein
receptor gene double knockout mice.
Key Words: antioxidants • coantioxidation • LDL • -tocopherol
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