Probucol protects lipoprotein (a) against oxidative modification.
Probucol, which decreases cholesterol levels and has antioxidant properties, was administered orally to patients with familial combined hyperlipidemia and high plasma lipoprotein(a) [Lp(a)] levels. The drug had no effect on Lp(a) concentrations after 4 weeks, but was found to be distributed in both Lp(a) and low-density lipoprotein (LDL). Before treatment, in each case LDL and Lp(a) isolated from the same individual were readily oxidized by copper, resulting in increased electrophoretic mobility and enhanced uptake and degradation by macrophages of both lipoproteins. After probucol treatment, both lipoproteins acquired resistance to in vitro oxidation by copper. Furthermore, probucol prevented their enhanced uptake and degradation by the macrophages. It is surmised that oxidized Lp(a) may carry an atherogenic potential that could be opposed by probucol administration.
Naruszewicz
M
M
Hyperlipidemia and Atherosclerosis Research Group, Clinical Research Institute of Montreal, Quebec, Canada.
Selinger
E
E
Dufour
R
R
Davignon
J
J
D000328:Adult; D001161:Arteriosclerosis / Q000517:prevention & control; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D005260:Female; D006801:Humans; D017270:Lipoprotein(a) / Q000737:chemistry / Q000378:metabolism*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010084:Oxidation-Reduction / Q000187:drug effects; D011341:Probucol / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D013997:Time Factors
D008078:Cholesterol, LDL; D017270:Lipoprotein(a); D002784:Cholesterol; D011341:Probucol