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

12 Citations (Scopus)

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

Fingerprint

Hepatectomy
Liver Transplantation
Extracellular Matrix
Oxidative Stress
Matrix Metalloproteinase 9
Phosphatidylinositol 3-Kinase
Liver
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinase-1
Matrix Metalloproteinase 2
Western Blotting
Protamine Kinase
Transplants
Cold Ischemia
Ataxia Telangiectasia
Proteins
Liver Regeneration
Matrix Metalloproteinase Inhibitors
Portal Hypertension
Reperfusion Injury

Keywords

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

ASJC Scopus subject areas

  • Hepatology

Cite this

Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats. / Hori, Tomohide; Uemoto, Shinji; Chen, Feng; Gardner, Lindsay B.; Baine, Ann Marie T; Hata, Toshiyuki; Kogure, Takayuki; Nguyen, Justin H.

In: World Journal of Hepatology, Vol. 6, No. 2, 02.2014, p. 72-84.

Research output: Contribution to journalArticle

Hori, Tomohide ; Uemoto, Shinji ; Chen, Feng ; Gardner, Lindsay B. ; Baine, Ann Marie T ; Hata, Toshiyuki ; Kogure, Takayuki ; Nguyen, Justin H. / Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats. In: World Journal of Hepatology. 2014 ; Vol. 6, No. 2. pp. 72-84.
@article{a4a58707611b4050b743747af2539fa0,
title = "Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats",
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.",
keywords = "Akt, Free radicals, Matrix metalloproteinase, Phosphatidylinositol 3-kinase, Tissue inhibitors of metalloproteinase",
author = "Tomohide Hori and Shinji Uemoto and Feng Chen and Gardner, {Lindsay B.} and Baine, {Ann Marie T} and Toshiyuki Hata and Takayuki Kogure and Nguyen, {Justin H}",
year = "2014",
month = "2",
doi = "10.4254/wjh.v6.i72",
language = "English (US)",
volume = "6",
pages = "72--84",
journal = "World Journal of Hepatology",
issn = "1948-5182",
publisher = "Baishideng Publishing Group",
number = "2",

}

TY - JOUR

T1 - Oxidative stress and extracellular matrices after hepatectomy and liver transplantation in rats

AU - Hori, Tomohide

AU - Uemoto, Shinji

AU - Chen, Feng

AU - Gardner, Lindsay B.

AU - Baine, Ann Marie T

AU - Hata, Toshiyuki

AU - Kogure, Takayuki

AU - Nguyen, Justin H

PY - 2014/2

Y1 - 2014/2

N2 - 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.

AB - 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.

KW - Akt

KW - Free radicals

KW - Matrix metalloproteinase

KW - Phosphatidylinositol 3-kinase

KW - Tissue inhibitors of metalloproteinase

UR - http://www.scopus.com/inward/record.url?scp=84894427691&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84894427691&partnerID=8YFLogxK

U2 - 10.4254/wjh.v6.i72

DO - 10.4254/wjh.v6.i72

M3 - Article

AN - SCOPUS:84894427691

VL - 6

SP - 72

EP - 84

JO - World Journal of Hepatology

JF - World Journal of Hepatology

SN - 1948-5182

IS - 2

ER -