title: Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats.
abstract: OBJECTIVE
  To investigate oxidative stress (OS)-mediated damage and the behavior of extracellular matrices in various rat models because shear stress with portal hypertension and cold ischemia/warm reperfusion injury trigger the liver regeneration cascade after surgery. These injuries also cause fatal liver damage.
  
  
  METHODS
  Rats were divided into four groups according to the surgery performed: control; hepatectomy with 40% liver remnant (60% hepatectomy); orthotopic liver transplantation (OLT) with whole liver graft (100% OLT); and split OLT (SOLT) with 40% graft (40% SOLT). Survival was evaluated. Blood and liver samples were collected at 6 h after surgery. Biochemical and histopathological examinations were performed. OS-induced damage, 4-hydroxynonenal, ataxia-telangiectasia mutated kinase, histone H2AX, phosphatidylinositol 3-kinase (PI3K) and Akt were evaluated by western blotting. Behavior of extracellular matrices, matrix metalloproteinase (MMP)-9, MMP-2, tissue inhibitor of metalloproteinase (TIMP)-1 and TIMP-2 were also evaluated by western blotting and zymography.
  
  
  RESULTS
  Although 100% OLT survived, 60% hepatectomy and 40% SOLT showed poor survival. Histopathological, immunohistological, biochemical and protein assays revealed that 60% hepatectomy, 100% OLT and 40% SOLT showed liver damage. PI3K and Akt were decreased in 60% hepatectomy and 40% SOLT. For protein expression, 40% SOLT showed differences in MMP-9, MMP-2 and TIMP-2. TIMP-1 showed differences in 60% hepatectomy and 40% SOLT. For protein activity, MMP-9 demonstrated significant differences in 60% hepatectomy, 100% OLT and 40% SOLT.
  
  
  CONCLUSIONS
  Under conditions with an insufficient liver remnant, prevention of OS-induced damage via the Akt/PI3K pathway may be key to improve the postoperative course. MMP-9 may be also a therapeutic target after surgery.
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Tomohide
authors.initials: T
authors.lastname: Hori
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Uemoto
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Feng
authors.initials: F
authors.lastname: Chen
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Lindsay B
authors.initials: LB
authors.lastname: Gardner
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Ann-Marie T
authors.initials: AM
authors.lastname: Baine
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Hata
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kogure
authors.affiliation: Tomohide Hori, Shinji Uemoto, Division of Hepato-Biliary-Pancreatic and Transplant Surgery, Department of Surgery, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan.
authors.forename: Justin H
authors.initials: JH
authors.lastname: Nguyen
keywords: Akt; Free radicals; Matrix metalloproteinase; Phosphatidylinositol 3-kinase; Tissue inhibitors of metalloproteinase