Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation andatherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice
Pk. Witting et al., Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation andatherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice, FASEB J, 13(6), 1999, pp. 667-675
Antioxidants can inhibit atherosclerosis in animals, though it is not clear
whether this is due to the inhibition of aortic lipoprotein lipid (per)oxi
dation, Coantioxidants inhibit radical-induced, tocopherol-mediated peroxid
ation of lipids in lipoproteins through elimination of tocopheroxyl radical
. Here we tested the effect of the bisphenolic probucol metabolite and coan
tioxidant H 212/43 on atherogenesis in apolipoprotein E and low density lip
oprotein (LDL) receptor gene double knockout (apoE-/-;LDLr-/-) mice, and ho
w this related to aortic lipid (per)oxidation measured by specific HPLC ana
lyses. Dietary supplementation with H 212/43 resulted in circulating drug l
evels of similar to 200 mu M, increased plasma total cholesterol slightly a
nd decreased plasma and aortic a-tocopherol significantly relative to age-m
atched control mice. Treatment with H 212/43 increased the antioxidant capa
city of plasma, as indicated by prolonged inhibition of peroxyl radical-ind
uced, ex vivo lipid peroxidation. Aortic tissue from control apoE-/-;LDLr-/
- mice contained lipid hydro(pero)xides and substantial atherosclerotic les
ions, both of which were decreased strongly by supplementation of the anima
ls with H 212/43, The results show that a coantioxidant effectively inhibit
s in vivo lipid peroxidation and atherosclerosis in apoE-/-;LDLr-/- mice, c
onsistent with though not proving a causal relationship between aortic lipo
protein lipid oxidation and atherosclerosis in this model of the disease.