Composition and aggregational forms of biliary lipids in human bile after short-term administration of Taurohyodeoxycholic acid

Abstract

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.