Lifibrol increases hepatic cholesterol 7α‐hydroxylase activity in sprague‐dawley rats

Abstract

The hypocholesterolemic drug lifibrol was administered orally to Sprague-Dawley rats to determine its effects on lipoprotein cholesterol distribution and hepatic HMG-CoA reductase and cholesterol 7a-hydroxylase activities. The effects of lifibrol on those endpoints were compared with the effects of gemfibrozil and lovaytatin. When administered to either chow-fed or cholesterol-fed rats, lifibrol (25 or 50 mglkgiday) caused a redistribution of lipoprotein cholesterol such that HDL increased and VLDL+ LDL decreased significantly Gemfibroril (30 or 50 mgikglday) caused similar changes in lipoprotein cholesterol distribution. In contrast, lovastatin (10 mgikglday) decreased both HDL and VLDL+LDL in chow-fed animals, but had no effect in cholesterol-fed animals. Hepatic HMG-CoA reductase activity was increased in rats treated with lifibrol (50 rnglkgl day), gemfibrozil (50 mglkgiday), and lovastatin (10 mgikgiday). 1 he most significant finding is that lifibrol was the only drug that increased hepatic cholesterol 7a-hydroxylase activity. This observation in rats separates the mechanism of action of lifibrol from those of the HMG-CoA reductase inhibitors and the fibrates, and suggests that one mechanism ot action of litibrol is to enhance cholesterol elimination through conversion to bile acids.1994 b\'iley ~i s s Inc