Hydrophilic bile salts enhance differential distribution of sphingomyelin and phosphatidylcholine between micellar and vesicular phases: potential implications for their effects in vivo

Background/Aims: The hepatocyte canalicular membrane enter leaflet contains both phosphatidylcholine (PC) and sphingomyelin (SM). Normally, PC is the exclusive phospholipid in bile. We examined effects of bile salt hydrophobi city on cytotoxicity and on differential SM and PC distribution between det ergent-resistant aggregated vesicles (model for detergent-resistant canalic ular membrane) and mixed micelles or small unilamellar vesicles (representi ng lipid phases in bile). Methods: Aggregated vesicles were obtained by ultracentrifugation of choles terol-supersaturated model systems containing SM, PC and various bile salts , micelles by ultrafiltration and unilamellar vesicles by dialysis of the s upernatant. Erythrocyte hemolysis and lactate dehydrogenase release from Ca Co-2 cells upon incubation with various micelles were quantified. Results: Preferential SM distribution and lipid solubilization in aggregate d vesicles increased in rank order taurodeoxycholate < taurocholate < tauro ursodeoxycholate < taurohyodeoxycholate, with reciprocal PC enrichment in m icelles and small unilamellar vesicles. Including small amounts of PC withi n taurohyodeoxycholate micelles increased cytotoxicity with more erythrocyt e hemolysis and LDH release from CaCo-2 cells upon incubation, but decrease d cytotoxicity in case of tauroursodeoxycholate micelles. Conclusions: Hydrophilic but not hydrophobic bile salts preserve integrity of pathophysiologically relevant phosphatidylcholine plus sphingomyelin-con taining bilayers. Enhanced biliary phospholipid secretion during taurohyode oxycholate but not during tauroursodeoxycholate therapy (Hepatology 25 (199 7) 1306) may relate to different interactions of these bile salts with phos pholipids. (C) 2001 European Association for the Study of the Liver. Publis hed by Elsevier Science B.V. All rights reserved.