HDL biology
Probucol and bezafibrate change HDL-cholesterol in cholesterol-fed rabbits via CETP activity, not liver CETP mRNA (Jpn Circ J 1999)
Original title: Combined effects of probucol and benzafibrate on lipoprotein metabolism and liver cholesteryl ester transfer protein mRNA in cholesterol-fed rabbits
Forty-nine cholesterol-fed Japanese White rabbits were divided into five groups (normal chow, cholesterol alone, cholesterol plus probucol, cholesterol plus bezafibrate, or cholesterol plus both drugs) and treated for eight weeks, with CETP activity in lipoprotein-deficient plasma and liver CETP mRNA measured by Northern blotting. HDL-cholesterol rose with bezafibrate (P<0.01) but fell with probucol and probucol-plus-bezafibrate (P<0.05), with no difference between the two probucol groups. CETP activity increased in the cholesterol, cholesterol-plus-probucol, and cholesterol-plus-probucol-plus-bezafibrate groups, but fell significantly in the cholesterol-plus-bezafibrate group, responding more sensitively to drug treatment than serum HDL-cholesterol did. Liver CETP mRNA levels, however, showed no changes among any of the five groups. The authors conclude that probucol and bezafibrate alter HDL-cholesterol through changes in CETP activity rather than liver CETP mRNA expression, and that bezafibrate could not reverse the HDL-lowering effect of probucol.
Original abstract
Probucol decreases and bezafibrate increases plasma high density lipoprotein-cholesterol (HDL-C) levels in humans. This study was performed to determine whether the HDL-C-lowering effects of probucol could be reversed by treatment with bezafibrate in hypercholesterolemic rabbits. Forty-nine normolipidemic Japanese White rabbits were divided into 5 groups [group 1: normal chow; group 2: 0.2% cholesterol (Ch) diet; group 3: 0.2% Ch and 1% probucol diet; group 4: 0.2% Ch and 1% bezafibrate diet; group 5: 0.2% Ch and 1% probucol plus 1% bezafibrate diet] and treated for 8 weeks. Plasma lipids, cholesteryl ester transfer protein (CETP) activity in the lipoprotein-deficient plasma fraction, CETP mRNA in liver tissue and plasma drug concentrations were investigated. Serum total cholesterol (TC) increased after the rabbits in groups 2, 3, 4 and 5 were fed Ch, but overall, no significant differences were observed in serum TC and triglyceride (TG) among these groups. Serum HDL-C levels increased (p<0.01) in the bezafibrate-treated group, but a significant (p<0.05) reduction in HDL-C was observed in both the Ch + probucol (group 3) and Ch + probucol plus bezafibrate (group 5) groups; no significant difference was observed between groups 3 and 5. Significant correlation (p<0.01) was found between serum low density lipoprotein cholesterol (LDL-C) levels and plasma probucol concentrations in groups 3 and 5, but no correlation was found between plasma concentrations of probucol/bezafibrate and serum HDL-C levels. CETP activity in the lipoprotein-deficient plasma fraction increased in the Ch-, Ch + probucol-, and Ch + probucol and bezafibrate-fed groups (groups 2, 3 and 5, respectively), whereas a significant reduction in this activity was observed in the Ch + bezafibrate-fed group (group 4). An analysis of covariance showed that the CETP activity responded more sensitively to drug treatment than did the serum HDL-C level. CETP mRNA in liver tissue was assessed by Northern blotting at 8 weeks, but no changes were observed among the 5 groups. Probucol decreased and bezafibrate increased serum HDL-C levels, through CETP activity without affecting liver CETP mRNA levels, and the decrease in HDL-C levels produced by probucol could not be reversed by bezafibrate.
Summary written by cetpinhibition.org from the published abstract; figures as published. Page updated 19 August 2026. Methods.