title: Role of glutathione in hepatic bile formation during reperfusion after cold ischemia of the rat liver.
abstract: OBJECTIVE
  Liver reperfusion following cold ischemia is frequently associated with diminished bile flow in patients undergoing liver transplantation. Glutathione is a major determinant of bile-acid independent bile flow, and the effects of cold ischemia on biliary glutathione excretion are unknown.
  
  
  METHODS
  We examined the effects of cold ischemia (University of Wisconsin solution (4 degrees C), 24 h) with subsequent reperfusion (100 min) on biliary glutathione excretion in a recirculating system. Since glutathione might represent an important antioxidant within the biliary tract and oxidative stress in the biliary tract during reperfusion could contribute to the pathogenesis of bile duct injury after liver transplantation, we also assessed bile duct morphology in reperfused livers of mutant TR- -rats, in whom biliary excretion of glutathione is already impaired.
  
  
  RESULTS
  Hepatic bile formation was diminished in reperfused Wistar rat livers after cold ischemia. Biliary glutathione concentrations and output were significantly decreased and correlated with postischemic changes in bile secretion. An increased biliary oxidized glutathione/glutathione ratio, indicating oxidative stress, was detected only immediately after the onset of reperfusion. Basal bile flow rates in TR- -rat livers which were already markedly reduced in control-perfused livers, decreased further during the early but not the later reperfusion period. Reperfusion of both Wistar and TR- -rat livers was not associated with electron microscopic evidence of bile duct damage.
  
  
  CONCLUSIONS
  We conclude that impaired biliary excretion of glutathione contributes to decreased bile flow after cold ischemia. The absence of biliary glutathione does not appear to promote ultrastructural evidence of bile duct injury during reperfusion in the isolated perfused rat liver.
authors.affiliation: Department of Internal Medicine and Liver Center, Yale University School of Medicine, New Haven, CT 06520-8019, USA.
authors.forename: T A
authors.initials: TA
authors.lastname: Koeppel
authors.forename: M
authors.initials: M
authors.lastname: Trauner
authors.forename: A
authors.initials: A
authors.lastname: Mennone
authors.forename: M
authors.initials: M
authors.lastname: Arrese
authors.forename: L
authors.initials: L
authors.lastname: Rios-Velez
authors.forename: J L
authors.initials: JL
authors.lastname: Boyer
mesh_terms: D000241:Adenosine; D000493:Allopurinol; D000818:Animals; D001646:Bile / Q000378:metabolism*; D001652:Bile Ducts / Q000502:physiology / Q000648:ultrastructure*; D003080:Cold Temperature; D005978:Glutathione / Q000378:metabolism / Q000502:physiology*; D066298:In Vitro Techniques; D007328:Insulin; D007511:Ischemia / Q000503:physiopathology*; D008099:Liver / Q000098:blood supply / Q000502:physiology*; D008297:Male; D009926:Organ Preservation; D019188:Organ Preservation Solutions; D011887:Raffinose; D051381:Rats; D017208:Rats, Wistar; D012044:Regression Analysis; D015424:Reperfusion; D013997:Time Factors
chemical_list: D007328:Insulin; D019188:Organ Preservation Solutions; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose