Enrichment of canalicular membrane with cholesterol and sphingomyelin prevents bile salt-induced hepatic damage
Date
1999
Journal Title
Journal ISSN
Volume Title
Publisher
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
Abstract
These studies were undertaken to characterize the role of plasma membrane cholesterol in canalicular secretory functions and hepatocyte integrity against intravenous taurocholate administration. Cholesterol and sphingomyelin concentrations and cholesterol/phospholipid ratios were significantly increased in canalicular membranes of diosgenin-fed rats, suggesting a more resistant structure against solubilization by taurocholate. During taurocholate infusion, control rats had significantly decreased bile flow, whereas diosgenin-fed animals maintained bile flow, Maximal cholesterol output increased by 176% in diosgenin-fed rats, suggesting an increased precursor pool of biliary cholesterol in these animals. Maximal phospholipid output only increased by 43% in diosgenin-fed rats, whereas bile salt output remained at control levels. The kinetics of glutamic oxalacetic: transaminase, lactic dehydrogenase, and alkaline phosphatase activities in bile showed a significantly faster release in control than in diosgenin-fed rats, After 30 min of hp travenous taurocholate infusion, necrotic hepatocytes were significantly increased in control animals.jlr Preservation of bile secretory functions and hepatocellular cytoprotection by diosgenin against the intravenous infusion of toxic doses of taurocholate was associated with an increased concentration of cholesterol and sphingomyelin in the canalicular membrane. The increase of biliary cholesterol output induced by diosgenin was correlated to the enhanced concentration of cholesterol in the canalicular membrane.
Description
Keywords
biliary lipids, cholesterol, bile salts, plasma membrane, membrane lipids, canaliculus, cytoprotection, sphingomyelin, maximal secretory rates, diosgenin, BILIARY LIPID SECRETION, STEROL CARRIER PROTEIN-2, P-GLYCOPROTEIN GENE, RAT-LIVER, HOMOZYGOUS DISRUPTION, PLASMA-MEMBRANE, CELL-DAMAGE, TRANSPORT, METABOLISM, MDR2