Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

Tomohide Hori, Shinji Uemoto, Feng Chen, Lindsay B. Gardner, Ann Marie T. Baine, Toshiyuki Hata, Takayuki Kogure, Justin H. Nguyen

Research output: Contribution to journalArticle

13 Scopus citations

Abstract

Aim: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)72-84
Number of pages13
JournalWorld Journal of Hepatology
Volume6
Issue number2
DOIs
StatePublished - Feb 2014

Keywords

  • Akt
  • Free radicals
  • Matrix metalloproteinase
  • Phosphatidylinositol 3-kinase
  • Tissue inhibitors of metalloproteinase

ASJC Scopus subject areas

  • Hepatology

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