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 crytalline 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 > or = 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.
Angelico
M
M
Dept. of Public Health, Tor Vergata University, Rome, Italy.
Mogavero
L
L
Baiocchi
L
L
Nistri
A
A
Gandin
C
C
D002756:Cholagogues and Choleretics / Q000737:chemistry / Q000627:therapeutic use*; D002769:Cholelithiasis / Q000737:chemistry / Q000188:drug therapy*; D002784:Cholesterol / Q000032:analysis; D004338:Drug Combinations; D004353:Drug Evaluation, Preclinical; D006801:Humans; D006863:Hydrogen-Ion Concentration; D010713:Phosphatidylcholines / Q000627:therapeutic use*; D013655:Taurochenodeoxycholic Acid / Q000737:chemistry / Q000627:therapeutic use*; D013657:Taurodeoxycholic Acid / Q000031:analogs & derivatives* / Q000737:chemistry / Q000627:therapeutic use*
D002756:Cholagogues and Choleretics; D004338:Drug Combinations; D010713:Phosphatidylcholines; C083510:taurohyodeoxycholic acid; D013655:Taurochenodeoxycholic Acid; D013657:Taurodeoxycholic Acid; C031655:ursodoxicoltaurine; D002784:Cholesterol