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Effect of Pirfenidone on Endotoxin-induced Liver Injury after Partial Hepatectomy in Rats

Research Project

Project/Area Number 16591373
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Digestive surgery
Research InstitutionKansai Medical University

Principal Investigator

KAIBORI Masaki  Kansai Medical University, Faculty of medicine, Instructor, 医学部, 助手 (30333199)

Co-Investigator(Kenkyū-buntansha) KAMIYAMA Yasuo  Kansai Medical University, Faculty of medicine, Professor, 医学部, 教授 (90127069)
KON Masanori  Kansai Medical University, Faculty of medicine, Associate Professor, 医学部, 助教授 (70225605)
Project Period (FY) 2004 – 2006
Project Status Completed (Fiscal Year 2006)
Budget Amount *help
¥3,500,000 (Direct Cost: ¥3,500,000)
Fiscal Year 2006: ¥1,000,000 (Direct Cost: ¥1,000,000)
Fiscal Year 2005: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2004: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsPirfenidone / Endotoxin / Hepatectomy / Pirfenidone / 肝虚血再灌流障害 / 肝切除後エンドトキシン血症 / 生体保護効果
Research Abstract

Background. In living donor liver transplantation, restrictions on graft size are a serious obstacle for the expansion of indications for adult recipients. The sequence of gram-negative infection, septicemia, and multiple organ failure is the most common cause of early mortality after liver transplantation. An effective therapy is not still established in endotoxemia following extended hepatectomy in donor or small for size graft in recipient. Pirfenidone (PFD) is a new experimental drug used as an antifibrotic agent. We investigated the effect of PFD on endotoxin-induced liver injury following partial hepatectomy.
Methods. Male Sprague-Dawley rats were intravenously administered with lipopolysaccharide (LPS) 48 h after 70% hepatectomy. Prior to LPS administration, PFD (300 mg/kg) or its vehicle (0.5% carboxymethylcellulose) was given orally twice.
Results. The survival rate of the PFD-treated group was markedly improved as compared with that of controls. PFD prevented the increases in activities of serum enzymes (AST, ALT, LDH) and total bilirubin. The levels of inflammatory cytokines such as tumor necrosis factor-α, interleukin-1β interferon-γ and interleukin-6 in serum and liver tissue were significantly lower in the PFD-treated group than in the control group. Furthermore, the degree of necrosis in remnant liver significantly decreased in the PFD-treated rats as compared with controls.
Conclusion. These results indicate that PFD alleviates endotoxin-induced liver injury after partial hepatectomy through the inhibition of production of inflammatory cytokines in the remaining liver. PFD may be useful to prevent endotoxin-induced liver injury after hepatectomy.

Report

(4 results)
  • 2006 Annual Research Report   Final Research Report Summary
  • 2005 Annual Research Report
  • 2004 Annual Research Report
  • Research Products

    (38 results)

All 2006 2005 2004

All Journal Article (38 results)

  • [Journal Article] Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in fats.2006

    • Author(s)
      Tsuji K, Kwon AH
    • Journal Title

      J Hepatol 42(1)

      Pages: 94-101

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Influence of transcatheter arterial chemoembolization on the prognosis after hepatectomy for hepatocellular carcinoma in patients with severe liver dysfunction.2006

    • Author(s)
      Kaibori M, Tanigawa N
    • Journal Title

      Anticancer Res 26(5B)

      Pages: 3685-3692

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recurrent hepatitis C after living donor liver transplantation detected by Tc-99m GSA liver scintigraphy.2006

    • Author(s)
      Kaibori M, Ha-Kawa SK
    • Journal Title

      Dig Dis Sci 51(11)

      Pages: 2013-2017

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) is useful for judging the safety of hepatic resection.2006

    • Author(s)
      Kwon AH, Matsui Y
    • Journal Title

      Surgery 140(3)

      Pages: 379-386

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of limited and anatomic hepatic resection for hepatocellular carcinoma with hepatitis C.2006

    • Author(s)
      Kaibori M, Matsui Y
    • Journal Title

      Surgery 139(3)

      Pages: 385-394

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor stimulates the induction of cytokine-induced neutrophil chemoattractant through the activation of NF-kappaB in rat hepatocytes.2006

    • Author(s)
      Kaibori M, Yanagida H
    • Journal Title

      J Surg Res 130(1)

      Pages: 88-93

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Administration of rhHGF-activator via portal vein stimulates the regeneration of cirrhotic liver after partial hepatectomy in rats.2006

    • Author(s)
      Yanagida H, Kaibori M
    • Journal Title

      J Surg Res 130(1)

      Pages: 38-44

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Influence of transcatheter arterial chemoembolization on the prognosis after hepatectomy for hepatocellular carcinoma in patients with severe liver dysfunction.2006

    • Author(s)
      Kaibori M
    • Journal Title

      Anticancer Res. 26(5B)

      Pages: 3685-3692

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Recurrent hepatitis C after living donor liver transplantation detected by Tc-99m GSA liver scintigraphy.2006

    • Author(s)
      Kaibori M
    • Journal Title

      Dig Dis Sci. 51(11)

      Pages: 2013-2017

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Preoperative regional maximal removal rate of technetium-99m-galactosyl human serum albumin (GSA-Rmax) is useful for judging the safety of hepatic resection.2006

    • Author(s)
      Kwon AH
    • Journal Title

      Surgery. 140(3)

      Pages: 379-386

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Comparison of limited and anatomic hepatic resection for hepatocellular carcinoma with hepatitis C.2006

    • Author(s)
      Kaibori M
    • Journal Title

      Surgery. 139(3)

      Pages: 385-394

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Hepatocyte growth factor stimulates the induction of cytokine-induced neutrophil chemoattractant through the activation of NF-kappaB in rat hepatocytes.2006

    • Author(s)
      Kaibori M
    • Journal Title

      J Surg Res. 130(1)

      Pages: 88-93

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Administration of rhHGF-activator via portal vein stimulates the regeneration of cirrhotic liver after partial hepatectomy in rats.2006

    • Author(s)
      Yanagida H
    • Journal Title

      J Surg Res. 130(1)

      Pages: 38-44

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced production of interleukin 6 in peripheral blood monocytes stimulated with mucins secreted into the bloodstream.2005

    • Author(s)
      Yokoigawa N, Takeuchi N
    • Journal Title

      Clin Cancer Res 11(17)

      Pages: 6127-6132

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prognosis of hepatocellular carcinoma after hepatectomy in patients with renal dysfunction.2005

    • Author(s)
      Kaibori M, Matsui Y
    • Journal Title

      World J Surg 29(3)

      Pages: 375-381

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Enhanced production of interleukin 6 in peripheral blood monocytes stimulated with mucins secreted into the bloodstream.2005

    • Author(s)
      Yokoigawa N
    • Journal Title

      Clin Cancer Res. 1;11(17)

      Pages: 6127-6132

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Prognosis of hepatocellular carcinoma after hepatectomy in patients with renal dysfunction.2005

    • Author(s)
      Kaibori M
    • Journal Title

      World J Surg. 29(3)

      Pages: 375-381

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Free radical scavenger (edaravone) prevents endotoxin-induced liver injury after partial hepatectomy in rats.2005

    • Author(s)
      Tsuji K
    • Journal Title

      J Hepatol. 42(1)

      Pages: 94-101

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pirfenidone inhibits the induction of iNOS stimulated by interleukin-1beta at a step of NF-kappaB DNA binding in hepatocytes.2004

    • Author(s)
      Nakanishi H, Kaibori M
    • Journal Title

      J Hepatol 41(5)

      Pages: 730-736

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of pirfenidone on induction of chemokines in rat hepatocytes.2004

    • Author(s)
      Kaibori M, Yanagida H
    • Journal Title

      Transplant Proc 36(7)

      Pages: 1980-1984

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of hepatocyte growth factor on induction of cytokine-induced neutrophil chemoattractant in rat hepatocytes.2004

    • Author(s)
      Kaibori M, Yanagida H
    • Journal Title

      Transplant Proc 36(7)

      Pages: 1977-1979

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of pirfenidone on endotoxin-induced liver injury after partial hepatectomy in rats.2004

    • Author(s)
      Kaibori M, Yanagida H
    • Journal Title

      Transplant Proc 36(7)

      Pages: 1975-1976

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats.2004

    • Author(s)
      Kaibori M, Yanagida H
    • Journal Title

      Transplant Proc 36(7)

      Pages: 1973-1974

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of inducible nitric oxide synthase in hepatocytes isolated from rats with ischemia-reperfusion injury.2004

    • Author(s)
      Yanagida H, Kaibori M
    • Journal Title

      Transplant Proc 36(7)

      Pages: 1962-1964

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cycloprodigiosin up-regulates inducible nitric oxide synthase gene expression in hepatocytes stimulated by interleukin-1beta.2004

    • Author(s)
      Teshima S, Nakanishi H
    • Journal Title

      Nitric Oxide 11(1)

      Pages: 9-16

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Preoperative chemolipiodolization of the whole liver for hepatocellular carcinoma.2004

    • Author(s)
      Kaibori M, Tanigawa N
    • Journal Title

      Anticancer Res 24(3b)

      Pages: 1929-1933

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Positive status of alpha-fetoprotein and des-gamma-carboxy prothrombin : important prognostic factor for recurrent hepatocellular carcinoma.2004

    • Author(s)
      Kaibori M, Matsui Y
    • Journal Title

      World J Surg 28(7)

      Pages: 702-707

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes.2004

    • Author(s)
      Teshima S, Nakanishi H
    • Journal Title

      J Hepatol 40(4)

      Pages: 616-623

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pirfenidone inhibits the induction of iNOS stimulated by interleukin-lbeta at a step of NF-kappaB DNA binding in hepatocytes.2004

    • Author(s)
      Nakanishi H
    • Journal Title

      J Hepatol. 41(5)

      Pages: 730-736

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of pirfenidone on induction of chemokines in rat hepatocytes.2004

    • Author(s)
      Kaibori M
    • Journal Title

      Transplant Proc. 36(7)

      Pages: 1980-1984

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effect of hepatocyte growth factor on induction of cytokine-induced neutrophil chemoattractant in rat hepatocytes.2004

    • Author(s)
      Kaibori M
    • Journal Title

      Transplant Proc. 36(7)

      Pages: 1977-1979

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Effects of pirfenidone on endotoxin-induced liver injury after partial hepatectomy in rats.2004

    • Author(s)
      Kaibori M
    • Journal Title

      Transplant Proc. 36(7)

      Pages: 1975-1976

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Pirfenidone protects endotoxin-induced liver injury after hepatic ischemia in rats.2004

    • Author(s)
      Kaibori M
    • Journal Title

      Transplant Proc. 36(7)

      Pages: 1973-1974

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Induction of inducible nitric oxide synthase in hepatocytes isolated from rats with ischemia-reperfusion injury.2004

    • Author(s)
      Yanagida H
    • Journal Title

      Transplant Proc. 36(7)

      Pages: 1962-1964

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Cycloprodigiosin up-regulates inducible nitric oxide synthase gene expression in hepatocytes stimulated by interleukin-lbeta.2004

    • Author(s)
      Teshima S
    • Journal Title

      Nitric Oxide. 11(1)

      Pages: 9-16

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Preoperative chemolipiodolization of the whole liver for hepatocellular carcinoma.2004

    • Author(s)
      Kaibori M
    • Journal Title

      Anticancer Res. 24(3b)

      Pages: 1929-1933

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Positive status of alpha-fetoprotein and des-gamma-carboxy prothrombin : important prognostic factor for recurrent hepatocellular carcinoma.2004

    • Author(s)
      Kaibori M
    • Journal Title

      World J Surg. 28(7)

      Pages: 702-707

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary
  • [Journal Article] Up-regulation of IL-1 receptor through PI3K/Akt is essential for the induction of iNOS gene expression in hepatocytes.2004

    • Author(s)
      Teshima S
    • Journal Title

      J Hepatol. 40(4)

      Pages: 616-623

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2006 Final Research Report Summary

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Published: 2004-04-01   Modified: 2016-04-21  

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