Distribution of cholesterol between vesicles and micelles in human gallbladder bile: Influence of treatment with chenodeoxycholic acid and ursodeoxycholic acid

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. (HEPATOLOGY 1991;13:104–110).

[1]  E. Wachtel,et al.  Phospholipid lamellae are cholesterol carriers in human bile. , 1990, Biochimica et biophysica acta.

[2]  Z. Halpern,et al.  Biliary micellar cholesterol nucleates via the vesicular pathway. , 1989, Biochimica et biophysica acta.

[3]  D. Jüngst,et al.  Association between cholesterol‐phospholipid vesicles and cholesterol crystals in human gallbladder bile , 1989, Hepatology.

[4]  Z. Halpern,et al.  Cholesterol nucleation from its carriers in human biles , 1988, Hepatology.

[5]  S. Gallinger,et al.  Vesicular cholesterol in bile. Relationship to protein concentration and nucleation time. , 1988, Biochimica et biophysica acta.

[6]  S. Strasberg,et al.  Nucleation of cholesterol from vesicles isolated from bile of patients with and without cholesterol gallstones. , 1987, Biochimica et biophysica acta.

[7]  F. Nervi,et al.  Ultracentrifugal isolation of vesicular carriers of biliary cholesterol in native human and rat bile , 1987, Hepatology.

[8]  E. Kaler,et al.  Partial characterization of a nonmicellar system of cholesterol solubilization in bile. , 1987, The American journal of physiology.

[9]  G. Tint,et al.  Effect of ursodeoxycholic acid and chenodeoxycholic acid on cholesterol and bile acid metabolism. , 1986, Gastroenterology.

[10]  B. Chapman,et al.  Distribution of biliary cholesterol between mixed micelles and nonmicelles in relation to fasting and feeding in humans. , 1986, Gastroenterology.

[11]  Z. Halpern,et al.  Vesicle aggregation in model systems of supersaturated bile: relation to crystal nucleation and lipid composition of the vesicular phase. , 1986, Journal of lipid research.

[12]  Z. Halpern,et al.  Factors affecting cholesterol monohydrate crystal nucleation time in model systems of supersaturated bile. , 1985, Journal of lipid research.

[13]  T. Gilat,et al.  Contribution of vesicular and micellar carriers to cholesterol transport in human bile. , 1985, Journal of lipid research.

[14]  N. Pattinson,et al.  Solubilisation of cholesterol in human bile , 1985, FEBS letters.

[15]  T. Gilat,et al.  A non‐micellar mode of cholesterol transport in human bile , 1983, FEBS letters.

[16]  M. Carey,et al.  Cholesterol gallstone dissolution in bile. Dissolution kinetics of crystalline cholesterol monohydrate by conjugated chenodeoxycholate-lecithin and conjugated ursodeoxycholate-lecithin mixtures: dissimilar phase equilibria and dissolution mechanisms. , 1983, Journal of lipid research.

[17]  N. Mazer,et al.  Quasi-elastic light-scattering studies of aqueous biliary lipid systems. Cholesterol solubilization and precipitation in model bile solutions. , 1983, Biochemistry.

[18]  A. Cooperman,et al.  Nucleation time: a key factor in the pathogenesis of cholesterol gallstone disease. , 1979, Gastroenterology.

[19]  K. Einarsson,et al.  Biliary lipid composition during treatment with different hypolipidaemic drugs * , 1979, European journal of clinical investigation.

[20]  M. Carey.  Critical tables for calculating the cholesterol saturation of native bile. , 1978, Journal of lipid research.

[21]  D. Small,et al.  The physical chemistry of cholesterol solubility in bile. Relationship to gallstone formation and dissolution in man. , 1978, The Journal of clinical investigation.

[22]  L. Barbara,et al.  Enzymatic determination of cholesterol in bile. , 1975, Clinica chimica acta; international journal of clinical chemistry.

[23]  D. Small,et al.  The physicochemical basis of cholesterol gallstone formation in man. , 1968, The Journal of clinical investigation.

[24]  A. Groen,et al.  Cholesterol nucleation and gallstone formation. , 1988, Journal of hepatology.

[25]  Z. Halpern,et al.  Rapid vesicle formation and aggregation in abnormal human biles. A time-lapse video-enhanced contrast microscopy study. , 1986, Gastroenterology.

[26]  O. Fausa,et al.  Quantitative determination of bile acids and their conjugates using thin-layer chromatography and a purified 3alpha-hydroxysteroid dehydrogenase. , 1974, Scandinavian journal of gastroenterology.