title: Inhibition by a coantioxidant of aortic lipoprotein lipid peroxidation and atherosclerosis in apolipoprotein E and low density lipoprotein receptor gene double knockout mice.
abstract: 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 approximately 200 microM, increased plasma total cholesterol slightly and decreased plasma and aortic alpha-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.
authors: Biochemistry Group, Heart Research Institute, Sydney, Australia.
authors: P K
authors: PK
authors: Witting
authors: K
authors: K
authors: Pettersson
authors: A M
authors: AM
authors: Ostlund-Lindqvist
authors: C
authors: C
authors: Westerlund
authors: A W
authors: AW
authors: Eriksson
authors: R
authors: R
authors: Stocker
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001011:Aorta / Q000187:drug effects*; D001057:Apolipoproteins E / Q000235:genetics*; D001161:Arteriosclerosis / Q000188:drug therapy*; D001559:Benzhydryl Compounds; D002784:Cholesterol / Q000097:blood; D015227:Lipid Peroxidation / Q000187:drug effects*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010636:Phenols / Q000097:blood / Q000494:pharmacology*; D011341:Probucol / Q000378:metabolism; D018110:Receptors, Lipoprotein / Q000235:genetics*; D014280:Triglycerides / Q000097:blood; D001713:Biphenyl Compounds
chemical_list: D000975:Antioxidants; D001057:Apolipoproteins E; D001559:Benzhydryl Compounds; D002784:Cholesterol; D010636:Phenols; D011341:Probucol; D018110:Receptors, Lipoprotein; D014280:Triglycerides; C404203:4,4'-bis(2,6-di-tert-butylphenol); D001713:Biphenyl Compounds