title: Endothelin-1 aggravates hepatic ischemia/reperfusion injury during obstructive cholestasis in bile duct ligated mice.
abstract: BACKGROUND
  Cholestasis of the liver is known to be an important risk factor for surgical morbidity and mortality after major hepatectomy. However, the mechanism of liver injury in cholestatic liver is not fully understood. The goal of this study was to investigate the process of liver injury due to hepatic ischemia/reperfusion in obstructive cholestasis.
  
  
  METHODS
  Male C57BL/6 mice underwent common bile duct ligation and subsequently developed obstructive cholestasis. The mice were subjected to 90 min of partial hepatic ischemia followed by reperfusion.
  
  
  RESULTS
  The survival rate of the mice with cholestatic livers after hepatic ischemia/reperfusion was lower than that of the mice with normal livers. Biochemical and histological analyses showed that the cholestatic mice had a much higher degree of hepatocellular injury after reperfusion than the normal mice. Neutrophil accumulation after reperfusion was significantly decreased in the cholestatic livers; however, considerable microcirculatory disturbances were observed in cholestatic livers after reperfusion. Hepatic stellate cell activation and hepatic expression of endothelin-1 were evaluated by immunohistochemical staining in cholestatic livers after reperfusion. These observations were also associated with increased serum levels of endothelin-1.
  
  
  CONCLUSIONS
  Hepatic stellate cell activation and increased endothelin-1 production play a crucial role in hepatic ischemia/reperfusion injury in cholestatic liver.
authors.affiliation: Department of General Surgery, Chiba University Graduate School of Medicine, Chiba, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Nagai
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kato
authors.forename: Fumio
authors.initials: F
authors.lastname: Kimura
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Shimizu
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshidome
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ohtsuka
authors.forename: Katsunori
authors.initials: K
authors.lastname: Furukawa
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nozawa
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Yoshitomi
authors.forename: Noboru
authors.initials: N
authors.lastname: Mitsuhashi
authors.forename: Dan
authors.initials: D
authors.lastname: Takeuchi
authors.forename: Kosuke
authors.initials: K
authors.lastname: Suda
authors.forename: Isaku
authors.initials: I
authors.lastname: Yoshioka
authors.forename: Masaru
authors.initials: M
authors.lastname: Miyazaki
mesh_terms: D000818:Animals; D019743:Chemokines, CXC / Q000378:metabolism; D002779:Cholestasis / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D003135:Common Bile Duct / Q000601:surgery; D019332:Endothelin-1 / Q000378:metabolism*; D055166:Hepatic Stellate Cells / Q000378:metabolism*; D008026:Ligation; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D015427:Reperfusion Injury / Q000276:immunology* / Q000378:metabolism
chemical_list: D019743:Chemokines, CXC; D019332:Endothelin-1