alpha-tocopherol and probucol reduce autoantibody titer to MDA-LDL in hypercholesterolemic rabbits

We considered the hypothesis that antioxidant supplementation that increase s aortic antioxidant concentrations would reduce autoantibody titer to MDA- LDL, a measure that may indicate in vivo oxidation. We assessed autoantibod y titer to NMA-LDL in rabbits before and after 5 months of treatment with a nutritionally adequate hypercholesterolemic diet alone (control) or supple mented with synthetic alpha -tocopherol or probucol. Aortic cholesterol and antioxidants were assessed at the end of treatment. alpha -Tocopherol supp lementation increased the ratio of aortic alpha -tocopherol to cholesterol by 20-30-fold, while probucol supplementation increased the ratio of aortic probucol to cholesterol to 4-13 mu mol/mol. Before treatment, MDA-LDL auto antibody titer averaged 5.09 +/- 0.24 with no difference among groups (p = .53 by ANOVA). However, after treatment, autoantibody titers differed among groups (p < .03 by ANOVA). Autoantibody titers were similar in rabbits sup plemented with alpha -tocopherol and probucol (3.69 +/- 0.21 and 3.73 +/- 0 .48, respectively, p = 0.81), and 26% (p < .009) lower in antioxidant suppl emented rabbits than unsupplemented hypercholesterolemic rabbits (5.03 +/- 0.47). There was an inverse J relationship between autoantibody titer after treatment and aortic alpha -tocopherol/cholesterol and probucol/cholestero l, with minimum values for autoantibody titers above 8-10 mu mol antioxidan t(mmol cholesterol. The results of this study are consistent with inhibitio n of in vivo intra-aortic oxidation when aortic alpha -tocopherol or probuc ol exceed 8-10 mu mol/mmol cholesterol. (C) 2001 Elsevier Science Inc.