COMPARISON OF EFFECTS OF PROBUCOL VERSUS VITAMIN-E ON EX-VIVO OXIDATION SUSCEPTIBILITY OF LIPOPROTEINS IN HYPERLIPOPROTEINEMIA

Oxidative modification of low-density lipoprotein (LDL) cholesterol ap pears to contribute to atherogenesis. Probucol reduces LDL cholesterol oxidation susceptibility, but the consistency, dose, and time course are not well described. Twelve hyperlipidemic patients were given prob ucol for 4 weeks at the usual dose for cholesterol reduction (1,000 mg /day), or one had (500 mg/day) or one quarter (250 mg/day) the usual d ose. Lipoprotein oxidation susceptibility of apolipoprotein B-containi ng lipoproteins was assessed using a rapid test in which LDL cholester ol and very-low-density lipoprotein are precipitated with dextran sulf ate and magnesium ions redissolved, incubated with copper ions for 3 h ours, and tested for thiobarbituric acid-reactive substances. Results are expressed as nmoles of malonyldialdehyde (MDA) generated per mg (n mol MDA/mg non-high-density lipoprotein cholesterol. Lipoproteins from probucol-treated patients become resistant to oxidation with a predru g value of 85+/-19, and decreasing to 3+/-1 nmol MDA/mg after drug ad ministration (p <0.001). Both ''half'' and ''full'' doses were effecti ve in lowering lipoprotein oxidation susceptibility by 95%. The ''quar ter'' dose was less effective. Oxidation inhibition was maximized with in 2 weeks, returning to baseline 4 to 6 weeks after discontinuing pro bucol. four patients were subsequently crossed over to vitamin E (1,20 0 IU/day). Vitamin E had a milder, less predictable antioxidant effect , lowering lipoprotein oxidation susceptibility by a mean of 24%. In c onclusion, probucol treatment effectively and predictably reduces plas ma lipoprotein susceptibility to ex vivo, copper-induced oxidation. Th is clinically applicable test may provide quantitation of antioxidant effects of probucol or other antioxidants and thus facilitate dose adj ustments and correlation with antiatherosclerotic effects.