Effect of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme a reductase inhibitor, on hepatic cholesterol 7α-hydroxylase, acyl-coenzyme A: cholesterol acyltransferase, and bile lipid secretion in the hamster with intact enterohepatic circulation

The effects of administration of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, on hepatic cholesterol 7α-hyroxylase and acyl-coenzyme A: cholesterol acyltransferase (ACAT) activities and bile lipid secretion were investigated in Syrian golden hamsters. Continuous administration of pravastatin induced no significant changes in hepatic cholesterol content, ACAT and cholesterol 7α-hydroxylase activities, or bile lipid and acid composition. Abrupt withdrawal of pravastatin induced increases in hepatic cholesterol content and ACAT activity and no change in hepatic cholesterol 7α-hydroxylase activity, and increased cholesterol saturation in bile. Hepatic cholesterol 7α-hydroxylase activity paralleled hepatic mRNA levels of this enzyme. These results suggest that a change in hepatic cholesterol metabolism induced by continuous administration of pravastatin maintains a constant net balance of hepatic cholesterol content. In addition, the drug has no deleterious influence on metabolism of bile lipids and acids and related enzymes, except for a transient increase in cholesterol saturation in bile induced by an inappropriate increase in hepatic cholesterol content and a lack of response of cholesterol 7α-hydroxylase activity to changes in hepatic cholesterol content upon abrupt withdrawal of pravastatin.