The Mechanism of Probucol Lowering Effects of High Density Lipoprotein

Abstract

Probucol reduces serum cholesterol level effectively even in patients with familial hypercholesterolemia. The long-term use of probucol enabled to show the regression of achilles tendon xanthoma and the first prevention of ischemic heart diseases. However, the mechanism of action lowering serum cholesterol is still obscure, and probucol also reduce HDL-cholesterol which has been believed to be a preventing factor against atherosclerosis. The aim of present study is to investigate the role of the liver in decreasing serum HDL-cholesterol during probucol administration. Probucol reduced VLDL-, LDL-, HDL₂ cholesterol and apoprotein A-I in both of HDL subfractions. When human apo B, E deficient HDL₃was iodinized and injected into portal vein, probucol accelerated the hepatic uptake of ¹²⁵I-HDL₂ in isolated perfused rat liver system and also in vivo. In vivo, its uptake of adrenal glands also increased significantly. Hepatic cholesterol concentration in treated rats showed slight increase in comparison to non-treated rats. We concluded that the increased uptake of HDL is one of causes of lowered serum HDL.