Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation andatherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice

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.