Alpha-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 alpha-tocopherol or probucol. Aortic cholesterol and antioxidants were assessed at the end of treatment. alpha-Tocopherol supplementation 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 micromol/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 alpha-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 alpha-tocopherol/cholesterol and probucol/cholesterol, with minimum values for autoantibody titers above 8-10 micromol antioxidant/mmol cholesterol. The results of this study are consistent with inhibition of in vivo intra-aortic oxidation when aortic alpha-tocopherol or probucol exceed 8-10 micro;mol/mmol cholesterol.
Schwenke
D C
DC
Department of Pathology, Wake Forest University School of Medicine, Winston-Salem, NC 27157-1072, USA. schwenke@wfubmc.edu
Behr
S R
SR
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D000975:Antioxidants / Q000032:analysis / Q000494:pharmacology; D001011:Aorta / Q000737:chemistry; D001161:Arteriosclerosis / Q000276:immunology; D001323:Autoantibodies / Q000097:blood*; D002784:Cholesterol / Q000032:analysis / Q000097:blood; D002791:Cholesterol, Dietary / Q000008:administration & dosage; D005260:Female; D006937:Hypercholesterolemia / Q000276:immunology*; D008077:Lipoproteins, LDL / Q000737:chemistry / Q000276:immunology*; D008315:Malondialdehyde / Q000494:pharmacology*; D011341:Probucol / Q000494:pharmacology*; D011817:Rabbits; D024502:alpha-Tocopherol / Q000494:pharmacology*
D000924:Anticholesteremic Agents; D000975:Antioxidants; D001323:Autoantibodies; D002791:Cholesterol, Dietary; D008077:Lipoproteins, LDL; D008315:Malondialdehyde; D002784:Cholesterol; D024502:alpha-Tocopherol; D011341:Probucol