THE INFLUENCE OF DIETARY CHOLESTEROL ON THE LITHOGENESITY OF BILE IN RATS TREATED WITH CLOFIBRA TE (II)

The HMG CoA reductase and cholesterol 7α-hydroxylase activities were determined and fecal bile acids were analyzed in rats fed with a low (0.16%) or a high (1%) cholesterol diet in order to investigate the influence of dietary cholesterol on the lithogenesity of bile in rats treated with clofibrate（α-p-chlorophenoxy isobutyl ethyl ester).　　The HMG CoA reductase activity displayed no change five days after administration of 200 mg/kg/day clofibrate to both the rats treated with a low or high cholesterol diet, although the activity fell considerably by administration of the cholesterol diet. But clofibrate produced a slight elevation of cholesterol 7α”hydroxylase activity in both diet groups.　　The fecal output of deoxycholic acid significantly increased in the rats fed with a low cholesterol diet but not in those fed with a high cholesterol diet after clofibrate administration.　　The foregoing results indicate the possibility that the enlarged poolsize of trihydroxy bile acids after clofibrate administration in the rats fed with a low cholesterol diet as seen in the previous experiment 1) will be due to the increased conversion of cholesterol into bile acids but not due to inhibition of bile acid output into feces.　　On the contrary, the absence of increase in the bile acid pool size in the rats fed with a high cholesterol diet after clofibrate administration 1) appeared to be due to deficiency of substrate in the liver. The substrate is meant to be the newly synthesized cholesterol in the liver, which was reduced by the feed back inhibition of exogenous cholesterol, and led to production of lithogenic bile with the aid of excess biliary cholesterol accelerated by another action of clofibrate.　　Clofibrate produced an increase in the liver weight of these animals, but failed to cause not only any light microscopic changes in the liver tissue but also any changes in the serum liver function tests.