Effect of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, on hepatic cholesterol 7 alpha-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 7 alpha-hydroxylase 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 7 alpha-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 7 alpha-hydroxylase activity, and increased cholesterol saturation in bile. Hepatic cholesterol 7 alpha-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 7 alpha-hydroxylase activity to changes in hepatic cholesterol content upon abrupt withdrawal of pravastatin.
Hayashi
K
K
First Department of Internal Medicine, Hiroshima University, School of Medicine, Japan.
Noshiro
M
M
Kurushima
H
H
Kuga
Y
Y
Nomura
S
S
Ohkura
Y
Y
Ohtani
H
H
Kurokawa
J
J
Tanaka
K
K
Yasunobu
Y
Y
D000818:Animals; D001646:Bile / Q000187:drug effects* / Q000378:metabolism; D001647:Bile Acids and Salts / Q000378:metabolism; D002790:Cholesterol 7-alpha-Hydroxylase / Q000187:drug effects / Q000378:metabolism*; D006224:Cricetinae; D008099:Liver / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008647:Mesocricetus; D008862:Microsomes, Liver / Q000201:enzymology; D017035:Pravastatin / Q000494:pharmacology*; D002785:Sterol O-Acyltransferase / Q000187:drug effects / Q000378:metabolism*
D001647:Bile Acids and Salts; D002790:Cholesterol 7-alpha-Hydroxylase; D002785:Sterol O-Acyltransferase; D017035:Pravastatin