Bile formation and biliary lipid composition under the influence of clofibrate and phenobarbital pretreatment in the rat.

Abstract

The effect of the two enzyme inducing agents, clofibrate and phenobarbital, on bile formation and biliary lipid composition was compared in male rats. Clofibrate (100 mg per kg body weight per day for 14 days) and phenobarbital (at first 60 mg per kg body weight per day for 3 days, then 100 mg per kg body weight per day for 11 days) increase the spontanous bile flow, the 14C-erythritol clearance but do not alter the bile salt excretion, indicating a stimulation of the bile acid independent fraction of bile. The bile of rats pretreated with clofibrate contains less cholesterol than the bile of saline treated control animals, whereas the concentrations of bile acids, phospholipids and cholesterol are reduced in the bile of the rats of the phenobarbital group. Both drugs diminish the cholesterol saturation of bile. If the biliary bile acid concentration and excretion are augmented by an infusion of sodium taurocholate (1000 nmol per min per 100 g body weight), the biliary concentration of cholesterol remains unchanged in the clofibrate group but increases in the phenobarbital group as compared with the saline control animals. The biliary phospholipid concentration is enhanced after clofibrate as well as after phenobarbital pretreatment. These studies indicate that the biliary excretion of cholesterol and phospholipids is at least to some extent regulated by the bile acid excretion. The importance of the synthesis of cholesterol and phospholipids for their biliary excretion, however, seems to be limited: a reduced cholesterol synthesis by clofibrate results in a reduced biliary cholesterol elimination. By contrast, an increased synthesis of cholesterol by phenobarbital and of the phospholipids by both drugs, however, may enlarge the intrahepatic lipid pools and may place more lipids available for biliary secretion.