Journal of Lipid Research, Vol 24, 461-468, Copyright © 1983 by Lipid Research, Inc.
Ursodeoxycholic acid treatment in cholesterol gallstone disease: effects on hepatic 3-hydroxy-3-methylglutaryl coenzyme A reductase activity, biliary lipid composition, and plasma lipid levels
B Angelin, S Ewerth and K Einarsson
The present study was undertaken to characterize the effects of
ursodeoxycholic acid on biliary lipid metabolism in man. Fifteen gallstone
patients were treated with ursodeoxycholic acid at a daily dosage of 15 mg
per kg body weight for about 4 weeks before cholecystectomy. At operation a
liver biopsy, together with gallbladder and hepatic bile, were obtained.
Eighteen untreated gallstone patients undergoing cholecystectomy served as
controls. During treatment with ursodeoxycholic acid, hepatic bile became
unsaturated with cholesterol in all patients investigated. The total
biliary lipid concentration remained unchanged. The hepatic cholesterol
concentration decreased by about 20%. No significant change in the
microsomal HMG CoA reductase activity was observed (38.5 +/- 6.7 pmol .
min-1 . mg protein-1 vs 38.3 +/- 4.7 pmol . min-1 . mg protein-1 in the
controls; means +/- SEM). Plasma concentrations of total cholesterol were
reduced by about 10%, and those of high density lipoprotein (HDL) and low
density lipoprotein (LDL) cholesterol by about 15%. Plasma triglyceride
levels remained essentially unchanged during treatment. We conclude that,
similar to chenodeoxycholic acid therapy, ursodeoxycholic acid treatment
results in unsaturation of fasting hepatic bile. In contrast to the changes
seen during chenodeoxycholic acid feeding, however, the unsaturation of
hepatic bile during ursodeoxycholic acid treatment is not primarily related
to a decreased hepatic HMG CoA reductase activity. Furthermore, while
chenodeoxycholic acid tends to increase plasma LDL levels, such changes are
not seen during ursodeoxycholic acid treatment.
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