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

Ludwig Amigo, Hegaly Mendoza, Silvana Zanlungo, Juan Francisco Miquel, Attilio Rigotti, Sergio González, Flavio Nervi

Research output: Contribution to journalArticlepeer-review

47 Citations (Scopus)

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 intravenons taurocholate infusion, necrotic hepatocytes were significantly increased in control animals. 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.

Original languageEnglish
Pages (from-to)533-542
Number of pages10
JournalJournal of Lipid Research
Volume40
Issue number3
Publication statusPublished - Mar 1999

Keywords

  • Bile salts
  • Biliary lipids
  • Canaliculus
  • Cholesterol
  • Cytoprotection
  • Diosgenin
  • Maximal secretory rates
  • Membrane lipids
  • Plasma membrane
  • Sphingomyelin

ASJC Scopus subject areas

  • Endocrinology
  • Cell Biology
  • Biochemistry

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