Effects of Ursodeoxycholic Acid on Synthesis of Cholesterol and Bile Acids in Healthy Subjects
- 1 October 2004
- journal article
- research article
- Published by S. Karger AG in Digestion
- Vol. 70 (2), 79-83
- https://doi.org/10.1159/000080925
Abstract
Background/Aims: Ursodeoxycholic acid (UDCA) decreases biliary secretion of cholesterol and is therefore used for the dissolution of cholesterol gallstones. It remains unclear whether these changes in biliary cholesterol excretion are associated with changes in cholesterol synthesis and bile acid synthesis. We therefore studied the activities of rate-limiting enzymes of cholesterol synthesis and bile acid synthesis, 3-hydroxy-3-methylglutaryl-coenzyme A reductase and cholesterol 7α-hydroxylase, respectively, in normal subjects during UDCA feeding. Methods: UDCA was given to 8 healthy volunteers (5 men, 3 women; age 24–44 years) in a single dose of 10–15 mg/kg body weight for 40 days. Before and during (days 3, 5, 10, 20, 30 and 40) UDCA treatment, urinary excretion of mevalonic acid and serum concentrations of 7α-hydroxy-4-cholesten-3-one (7α-HCO) were determined as markers of cholesterol and bile acid synthesis, respectively. The Wilcoxon signed rank test and Spearman’s rank correlation coefficient were used for statistical analysis. Results: Cholesterol synthesis and serum lipid concentrations remained unchanged during UDCA treatment for 40 days. However, synthesis of bile acids increased during long-term treatment with UDCA as reflected by an increase in 7α-HCO serum concentrations from 39.7 ± 21.3 ng/ml (median 32.8 ng/ml) before treatment to 64.0 ± 30.4 ng/ml (median 77.5 ng/ml) at days 30–40 of UDCA treatment (p < 0.05). Conclusions: UDCA treatment does not affect cholesterol synthesis in the liver, but does increase bile acid synthesis after prolonged treatment. This may represent a compensatory change following decreased absorption of endogenous bile acids as observed with UDCA therapy.Keywords
This publication has 13 references indexed in Scilit:
- Feedback regulation of bile acid synthesis in primary human hepatocytes: Evidence that CDCA is the strongest inhibitorJournal of Hepatology, 2003
- Effects of combined treatment with pravastatin and ursodeoxycholic acid on hepatic cholesterol metabolismEuropean Journal of Clinical Investigation, 2002
- Regulation of early cholesterol biosynthesis in rat liver: Effects of sterols, bile acids, lovastatin, and BM 15.766 on 3-hydroxy-3-methylglutaryl coenzyme A synthase and acetoacetyl coenzyme A thiolase activitiesJournal of Hepatology, 1998
- Serum concentrations of 7alpha-hydroxy-4-cholesten-3-one reflect bile acid synthesis in humansJournal of Hepatology, 1996
- Bile acids suppress the secretion of very-low-density lipoprotein by human hepatocytes in primary cultureJournal of Hepatology, 1996
- Regulation of bile acid synthesis by deoxycholic acid in the rat: Different effects on cholesterol 7?-hydroxylase and sterol 27-hydroxylase*1Journal of Hepatology, 1995
- Direct correlation between cholesterol synthesis and hepatic secretion of apolipoprotein B-100 in normolipidemic subjectsMetabolism, 1995
- The plasma level of 7α‐hydroxy‐4‐cholesten‐3‐one reflects the activity of hepatic cholesterol 7α‐hydroxylase in manFEBS Letters, 1991
- Morbidity and mortality from chronic hepatitis B virus infection in family members of patients with malignant and nonmalignant hepatitis B virus-related chronic liver diseasesJournal of Hepatology, 1991
- Levels of 7α‐hydroxy‐4‐cholesten‐3‐one in plasma reflect rates of bile acid synthesis in manFEBS Letters, 1988