The effect of probucol and vitamin E treatment on the oxidation of low-density lipoprotein and forearm vascular responses in humans.
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.
McDowell
I F
IF
Department of Clinical Biochemistry, Queen's University, Royal Victoria Hospital, Belfast, Northern Ireland.
Brennan
G M
GM
McEneny
J
J
Young
I S
IS
Nicholls
D P
DP
McVeigh
G E
GE
Bruce
I
I
Trimble
E R
ER
Johnston
G D
GD
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
D008078:Cholesterol, LDL; D000960:Hypolipidemic Agents; D014810:Vitamin E; D008148:Lovastatin; D019821:Simvastatin; D011341:Probucol