title: The effect of probucol and vitamin E treatment on the oxidation of low-density lipoprotein and forearm vascular responses in humans.
abstract: This study investigates the hypothesis that lipid soluble antioxidants may increase the resistance of low-density lipoprotein (LDL) to oxidation and also enhance vascular endothelial responses in humans. In a double-blind parallel group study, 24 hypercholesterolaemic patients already on treatment with simvastatin (20 mg day-1), were randomized to supplementary treatment with probucol (500 mg bd), vitamin E (400 IU daily) or placebo for 8 weeks. Mean serum cholesterol before antioxidant treatment was 7.00 mmol l-1. Resistance of LDL to oxidation by copper was increased by 830% in the probucol group and by 30% in the vitamin E group. However, thiobarbituric acid reacting substances in whole serum were not altered by either antioxidant. Probucol lowered HDL- and LDL-cholesterol levels and increased the QT interval. Forearm vascular responses, as measured by venous occlusion plethysmography, to acetylcholine, glyceryl trinitrate and NG-monomethyl-L-arginine, were not significantly changed by antioxidant treatment. Probucol has a major, and vitamin E a minor, effect on LDL resistance to oxidation but neither compound appears to alter forearm vascular responses in vivo.
authors.affiliation: Department of Clinical Biochemistry, Queen's University, Royal Victoria Hospital, Belfast, Northern Ireland.
authors.forename: I F
authors.initials: IF
authors.lastname: McDowell
authors.forename: G M
authors.initials: GM
authors.lastname: Brennan
authors.forename: J
authors.initials: J
authors.lastname: McEneny
authors.forename: I S
authors.initials: IS
authors.lastname: Young
authors.forename: D P
authors.initials: DP
authors.lastname: Nicholls
authors.forename: G E
authors.initials: GE
authors.lastname: McVeigh
authors.forename: I
authors.initials: I
authors.lastname: Bruce
authors.forename: E R
authors.initials: ER
authors.lastname: Trimble
authors.forename: G D
authors.initials: GD
authors.lastname: Johnston
mesh_terms: D000328:Adult; D008078:Cholesterol, LDL / Q000097:blood* / Q000187:drug effects; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D005542:Forearm / Q000098:blood supply*; D006801:Humans; D006949:Hyperlipidemias / Q000097:blood / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000008:administration & dosage; D008148:Lovastatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D011341:Probucol / Q000008:administration & dosage* / Q000009:adverse effects; D012039:Regional Blood Flow; D019821:Simvastatin; D014810:Vitamin E / Q000008:administration & dosage* / Q000009:adverse effects / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014810:Vitamin E; D008148:Lovastatin; D019821:Simvastatin; D011341:Probucol