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Distribution of cholesterol between vesicles and micelles in human gallbladder bile: Influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid
Author(s) -
Sahlin Staffan,
Thyberg Per,
Ahlberg Jon,
Angelin Bo,
Einarsson Kurt
Publication year - 1991
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.1840130115
Subject(s) - ursodeoxycholic acid , chenodeoxycholic acid , cholesterol , deoxycholic acid , gallbladder , chemistry , medicine , bile acid , phospholipid , gastroenterology , biochemistry , membrane
Abstract The present study aimed at determining the relative distribution of cholesterol between the vesicular and micellar phases in gallbladder bile of gallstone patients (n = 23) and gallstone‐free subjects (n = 7). Nine of the gallstone patients were treated with chenodeoxycholic acid and seven were treated with ursodeoxycholic acid, 15 mg/kg/day, for 3 wk before cholecystectomy. The vesicular and micellar fractions in bile were separated by sucrose density gradient ultracentrifugation, and a clear separation between the two phases was obtained. The vesicles were further identified by quasielastic light scattering spectroscopy and appeared to be of a uniform size with a mean hydrodynamic radius of 760 Å. The proportion of cholesterol in the vesicular fraction was significantly higher in the untreated gallstone group (40% ± 4%) compared with the gallstone‐free (28% ± 3%), ursodeoxycholic acid (28% ± 3%) and chenodeoxycholic acid (18%± 4%) groups. Despite a low cholesterol saturation of bile in the latter three groups (88% ± 12%, 51% ± 9% and 65% ± 5%, respectively), a considerable part of the biliary cholesterol was carried in the vesicular fraction. The cholesterol/phospholipid ratio in the vesicular fraction averaged between 0.49 and 0.58 in the gallstone, gallstone‐free and chenode‐oxycholic acid groups, whereas the ursodeoxycholic acid group had a significantly lower ratio of 0.24. The cholesterol/phospholipid ratio was about 0.15 in all micellar fractions. The nucleation time of bile from the gallstone group was short (2 ± 1 days) compared with the gallstone‐free, chenodeoxycholic acid and ursodeoxycholic acid groups (23 ± 3, 24 ± 6 and 14 ± 3 days, respectively). These observations give further support to the concept that the mechanism for gallstone dissolution is complex and different for chenodeoxycholic acid and ursodeoxycholic acid. (H EPATOLOGY 1991;13:104–110).