title: Large intravenous bilirubin loads increase the cytotoxicity of bile and lower the resistance of the canalicular membrane to cytotoxic injury and cause cholestasis in pigs.
abstract: BACKGROUND
  Large intravenous bilirubin loads cause loss of hepatic canalicular membrane microvilli and cholestasis. This study examines whether these untoward effects might be due to canalicular membrane injury from cytotoxic bile.
  
  
  METHODS
  The cytotoxicity of bile was assayed against pig erythrocytes before and throughout 4.5-h intravenous infusion of 170 microg kg(-1) body weight of bilirubin in anaesthetized pigs. The capacity to generate canalicular bile flow was tested before and after bilirubin infusion by means of short-term intraportal cholic acid infusion.
  
  
  RESULTS
  Bilirubin infusion increased the cytotoxicity of hepatic bile, reduced biliary phospholipid secretion by 90%, and caused cholestasis. Cholic acid infusion before bilirubin also increased the cytotoxicity of bile but increased bile flow and doubled biliary phospholipid output.
  
  
  CONCLUSIONS
  Large intravenous bilirubin infusions increase the cytotoxicity of bile, suppress biliary phospholipid secretion, and render hepatic canalicular membrane microvilli susceptible to injury from cytotoxic bile so that cholestasis occurs.
authors.affiliation: Institute for Experimental Medical Research and Research Forum, Ullevål Hospital, Oslo, Norway.
authors.forename: B A
authors.initials: BA
authors.lastname: Bjørnbeth
authors.forename: M
authors.initials: M
authors.lastname: Endresen
authors.forename: E
authors.initials: E
authors.lastname: Hvattum
authors.forename: T
authors.initials: T
authors.lastname: Lyberg
authors.forename: O
authors.initials: O
authors.lastname: Villanger
authors.forename: M G
authors.initials: MG
authors.lastname: Raeder
mesh_terms: D000818:Animals; D001646:Bile / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D001648:Bile Canaliculi / Q000187:drug effects / Q000473:pathology* / Q000648:ultrastructure; D001663:Bilirubin / Q000008:administration & dosage / Q000502:physiology*; D001706:Biopsy; D002462:Cell Membrane / Q000187:drug effects / Q000473:pathology*; D002779:Cholestasis / Q000139:chemically induced / Q000473:pathology*; D005434:Flow Cytometry; D008099:Liver / Q000473:pathology; D008855:Microscopy, Electron, Scanning; D008871:Microvilli / Q000187:drug effects / Q000473:pathology; D013552:Swine
chemical_list: D001663:Bilirubin