title: Bile acids protect the liver against the cholestatic effect of large bilirubin loads.
abstract: BACKGROUND
  This study was undertaken to elucidate why large bilirubin loads cause canalicular cholestasis and whether bile acid infusions protect against bilirubin-induced cholestasis.
  
  
  METHODS
  The effects of bilirubin infusion on canalicular bile secretion and canalicular membrane morphology were studied in bile acid-depleted pigs (BADP), bile acid-primed pigs (BAPP), and pigs co-infused with bile acids during bilirubin loading (BACIP).
  
  
  RESULTS
  Bilirubin caused complete cholestasis in BADP, 38% bile flow reduction in BAPP, and no effect on bile flow in BACIP. Scanning electron micrographs showed loss of 70% of canalicular microvilli in BADP, 13% loss and pathologic changes in the remaining 75% of microvilli in BAPP, and no canalicular changes in BACIP. Cholestasis was not due to hydromechanical obstruction of bile ductules or bile Ca2+ depletion.
  
  
  CONCLUSIONS
  Bilirubin causes cholestasis in BADP by injuring canalicular microvilli. Intravenous glycocholate infusions fully protect the liver against bilirubin-induced cholestasis and canalicular microvillar injury.
authors.affiliation: Institute for Experimental Medical Research, University of Oslo, Norway.
authors.forename: O
authors.initials: O
authors.lastname: Villanger
authors.forename: B A
authors.initials: BA
authors.lastname: Bjørnbeth
authors.forename: T
authors.initials: T
authors.lastname: Lyberg
authors.forename: M G
authors.initials: MG
authors.lastname: Raeder
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000627:therapeutic use*; D001648:Bile Canaliculi / Q000473:pathology*; D002779:Cholestasis / Q000188:drug therapy* / Q000209:etiology* / Q000473:pathology; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D006932:Hyperbilirubinemia / Q000150:complications*; D007262:Infusions, Intravenous; D008297:Male; D013552:Swine
chemical_list: D001647:Bile Acids and Salts