Dissolution of human cholesterol gallstones in bile salt lecithin mixtures: Effect of bile salt hydrophobicity and various pHs

Background: Unconjugated bile salts currently available for gallstone dissolution are poorly effective. We evaluated in vitro the litholytic potency of taurine-amidated bile salts against human cholesterol gallstones. Methods: Seventy radiolucent gallstones with similar size and composition (cholesterol content, 70.1 +/- 0.9%) from a single patient were incubated in model biles composed of 100 mM of either taurochenodeoxycholate (TCDC), taurocholate (TC), taurohyodeoxycholate (THDC) or tauroursodeoxycholate (TUDC) and of 45 mM egg yolk lecithin in saline buffered with tris/HCl (at pHs 7 and 8) or phosphate (at pHs 4 and 6). Biles (total lipids, 10 g/dl; cholesterol saturation, 99%) were incubated at 37 degrees C for 40 days. Gallstones were periodically weighed and returned to the dissolution vials, and the biliary cholesterol concentration was monitored. Results: Model biles remained optically clear during the initial 48 h of incubation. Then, biles containing THDC and TUDC, but not those with TC and TCDC, became progressively turbid until, after several days, a white precipitate surrounded the residual stone. Abundant liquid crystalline droplets were observed at polarizing microscopy in biles containing TUDC and THDC. Gallstone dissolution was closely related to cholesterol solubilization and decreased in the order TCDC > THDC greater than or equal to TC > TUDC, being highest at pH 8. At the physiologic pH of 7 THDC was more litholythic than TC. Conclusions: In vitro, the litholytic potency of bile salts on cholesterol gallstones primarily depends on their hydrophobicity. THDC is a new potential gallstone-dissolving agent, deserving in vivo studies.