Introduction: Taurohyodeoxycholic acid (THDC), a new natural hydrophilic bile salt, dissolves human cholesterol gallstones in vitro and may be effective as a litholytic agent in vivo. We thus, investigated in man the effects of short-term oral administration of THDC on lipid composition and physical-chemical features of bile. Methods: Three patients with a nasobiliary drainage (positioned after sphincterotomy for bile duct stones removal) were given 3 g of THDC (1 g every 12 h). At time of the study patients had an intact entero-hepatic circulation and minimal signs of cholestasis. Bile was collected before each THDC administration, the last sample being obtained 14 h after the final THDC dose. All specimens were analyzed for individual bile salts (HPLC) and lipids. Biliary lipid carriers were separated by gel-chromatography on Superose-6 and analyzed by quasielastic light scattering (QLS) and electron microscopy (EM). Results: biliary THDC concentration represented 30.3, 27.2 and 29.2% of total bile salts, respectively. Lecithin and cholesterol concentration in bile did not change significantly during the study. In all bile lipids were almost exclusively eluted in a single gel-chromatographic peak, with an average molecular weight between 20 and 100 kDa QLS analysis of THDC-rich biles, demonstrated an average hydrodynamic diameter of this lipid-carrier of 300 nm. In THDC-free biles fractionated using the same conditions, the predominant lipid-carrier had an average hydrodynamic diameter of 250 nm. This difference in size was confirmed at EM. Conclusions: THDC is efficiently secreted in human bile, without causing changes in the concentration of biliary lipids. The latter, however, are assembled in structures larger than those found in THDC-free biles. The size and spherical appearance of these aggregates are consistent with those of large unilamellar vesicles or multilamellar structures.
Baiocchi, L., Virgilio, C., Arancia, G., Cosentino, S., Calcabrini, A., Nistri, A., et al. (1997). Composition and aggregational forms of biliary lipids in human bile after short-term administration of Taurohyodeoxycholic acid. HEPATOLOGY RESEARCH, 7(3), 178-187 [10.1016/S0928-4346(97)00039-X].