Persistent effects of chenodeoxycholic acid on biliary lipids in the hamster

Abstract

The effects of feeding chenodeoxycholic acid (CDC) on biliary lipid composition, on the rate-limiting enzymes of hepatic cholesterol and bile acid synthesis, and on hepatic cholesterol and bile acids were determined in hamsters. The goals were to study the mechanism and duration of the cholesterol desaturation action of CDC. Administration of CDC for 30 days significantly increased the biliary bile acid and lecithin to cholesterol ratio and the percentage of CDC in bile (p less than 0.01). These effects persisted for 20 days after discontinuing CDC (p less than 0.01) and were no longer evident at 30 days. HMG CoA reductase and 7 alpha-hydroxylase activities were significantly reduced by CDC (p less than 0.01). After discontinuing CDC, these effects persisted for 10 days at which time HMG CoA reductase was still decreased by 50 per cent (p less than 0.01) and 7 alpha-hydroxylase by only 12 per cent (p less than 0.01) and were no longer evident by 20 days. Hepatic cholesterol did not change, while hepatic CDC was significantly elevated throughout the experiment.

Conclusions: (1) CDC has a salutory effect on biliary lipid composition while causing an increase of exogenous CDC in bile and a decrease of endogenous cholesterol synthesis. (2) The persistence of decreased cholesterol synthesis and of improved biliary lipid composistion after discontinuing CDC provides a rationale for studying this in man and then testing intermittent CDC regimes for gallstone dissolution.