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

We considered the hypothesis that antioxidant supplementation that increases aortic antioxidant concentrations would reduce autoantibody titer to MDA-LDL, a measure that may indicate in vivo oxidation. We assessed autoantibody titer to MDA-LDL in rabbits before and after 5 months of treatment with a nutritionally adequate hypercholesterolemic diet alone (control) or supplemented with synthetic α-tocopherol or probucol. Aortic cholesterol and antioxidants were assessed at the end of treatment. α-Tocopherol supplementation increased the ratio of aortic α-tocopherol to cholesterol by 20–30-fold, while probucol supplementation increased the ratio of aortic probucol to cholesterol to 4–13 μmol/mol. Before treatment, MDA-LDL autoantibody 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 supplemented with α-tocopherol and probucol (3.69 ± 0.21 and 3.73 ± 0.48, respectively, p = 0.81), and 26% (p < .009) lower in antioxidant supplemented rabbits than unsupplemented hypercholesterolemic rabbits (5.03 ± 0.47). There was an inverse J relationship between autoantibody titer after treatment and aortic α-tocopherol/cholesterol and probucol/cholesterol, with minimum values for autoantibody titers above 8–10 μmol antioxidant/mmol cholesterol. The results of this study are consistent with inhibition of in vivo intra-aortic oxidation when aortic α-tocopherol or probucol exceed 8–10 μmol/mmol cholesterol.