Enrichment of canalicular membrane with cholesterol and sphingomyelin prevents bile salt-induced hepatic damage

These studies were undertaken to characterize the role of plasma membrane c holesterol in canalicular secretory functions and hepatocyte integrity agai nst intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly incre ased in canalicular membranes of diosgenin-fed rats, suggesting a more resi stant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas dios genin-fed animals maintained bile flow, Maximal cholesterol output increase d by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only incr eased by 43% in diosgenin-fed rats, whereas bile salt output remained at co ntrol levels. The kinetics of glutamic oxalacetic: transaminase, lactic deh ydrogenase, and alkaline phosphatase activities in bile showed a significan tly faster release in control than in diosgenin-fed rats, After 30 min of h p travenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals.jlr Preservation of bile secretory functions a nd hepatocellular cytoprotection by diosgenin against the intravenous infus ion of toxic doses of taurocholate was associated with an increased concent ration of cholesterol and sphingomyelin in the canalicular membrane. The in crease of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.