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The mechanism of liver dysfunction in endogenous septic shock model mice

Research Project

Project/Area Number 15590402
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeSingle-year Grants
Section一般
Research Field Bacteriology (including Mycology)
Research InstitutionTokyo University of Pharmacy and Life Sciences

Principal Investigator

OHNO Naohito  Tokyo University of Pharmacy and Life Sciences, Pharmacy, Professor, 薬学部, 教授 (80152213)

Co-Investigator(Kenkyū-buntansha) ADACHI Yoshiyuki  Tokyo University of Pharmacy and Life Sciences, Pharmacy, Associate Professor, 薬学部, 助教授 (60222634)
MIURA Noriko  Tokyo University of Pharmacy and Life Sciences, Pharmacy, Assistant Professor, 薬学部, 講師 (30218036)
NAMEDA Sachiko  Tokyo University of Pharmacy and Life Sciences, Pharmacy, Assistant, 薬学部, 助手 (80339100)
Project Period (FY) 2003 – 2005
Project Status Completed (Fiscal Year 2005)
Budget Amount *help
¥3,600,000 (Direct Cost: ¥3,600,000)
Fiscal Year 2005: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2004: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2003: ¥2,400,000 (Direct Cost: ¥2,400,000)
Keywordssepsis / NSAIDs / beta-glucan / liver injury / nitric oxide / intestinal bacteria / antibiotics / βグルカン / 酸化窒素 / 敗血症性ショック
Research Abstract

Sepsis is a systemic inflammatory syndrome commonly caused by bacterial infection and is associated with multiple organ failure and dysfunction. Despite effective antibiotics, septic shock remains the high mortality. We have developed an animal model of sepsis in mice by repeatedly administering two drugs, indomethacin (IND) and β-glucan (BG). The combination of BG and IND induced severe lethality and increased the number of leukocytes in various organs and these cells were activated.
1. The livers of BG/IND treated mice were fixed in buffered formalin and stained with hematoxylin-eosin. The rate of nonparenchymal cell was increased in the livers of septic mice. BG/IND mice contained significantly higher numbers of bacteria than control mice in various organs. Moreover, TNF-α,MCP-1, and IL-6 concentrations of BG/IND administered mice in sera were enhanced. It suggested that severe damage and increased permeability of the gastrointestinal tract led to ulcers, inflammation of multiple organs and sepsis on administration of BG/IND.
2. The mice administered BG/IND produced a significant concentration of nitric oxide (NO) from peritoneal exuded cells (PEC) culture. To examine the effect of NO on the lethality, a NOS inhibitor, L-NAME was administered. L-NAME increased the mortality. Treatment with L-NAME and BG/IND enhanced production of IL-1β,IL-6 and TNF-α in PEC was significantly increased. The release of GOT and GPT was also increased in mice treated with the combination of L-NAME and BG/IND. It suggested that the production of NO has a protective effect in this model.
3. BG/IND administered mice treated with antibiotics prolonged the survival. Moreover, LPS elicited productions of inflammatory cytokines were decreased in sera of mice treated with antibiotics. These facts strongly suggested that the antibiotics treatment protected mice from the sensitization to LPS and thus reduced risk of sepsis, such as microbial translocation and leukocyte accumulation in the gut.

Report

(4 results)
  • 2005 Annual Research Report   Final Research Report Summary
  • 2004 Annual Research Report
  • 2003 Annual Research Report
  • Research Products

    (13 results)

All 2006 2005

All Journal Article (9 results) Book (4 results)

  • [Journal Article] Effect of nitric oxide on β-glucan/indomethacin-induced septic shock2005

    • Author(s)
      Sachiko Nameda, Maki Saito, Noriko N.Miura, Yoshiyuki Adachi, Naohito Ohno
    • Journal Title

      Biol. Pharm. Bull 28

      Pages: 1254-1258

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] 真菌β-1, 3-グルカン類の構造と宿主応答性2005

    • Author(s)
      大野 尚仁
    • Journal Title

      Dojin News 114

      Pages: 1-10

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of nitric oxide on β-glucan/indomethacin-induced septic shock2005

    • Author(s)
      Sachiko Nameda, Maki Saito, Noriko N.Miura, Yoshiyuki Adachi, Naohito Ohno
    • Journal Title

      Biol.Pharm.Bull. 28

      Pages: 1254-1258

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Structure and immunomodulating activity of fungal β-1,3-glucan2005

    • Author(s)
      Naohito Ohno
    • Journal Title

      Dojin News 114

      Pages: 1-10

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] β-glucan receptor (s) and their signal transduction2005

    • Author(s)
      Yoshiyuki Adachi
    • Journal Title

      Toxicology of 1→3-Beta-Glucans

      Pages: 95-108

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Fate of β-glucans in vivo : organ distribution and degradation mechanisms of fungal β-glucans in the body2005

    • Author(s)
      Noriko N.Miura
    • Journal Title

      Toxicology of 1→3-Beta-Glucans

      Pages: 109-126

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Endogenous septic shock by combination of β-glucan and NSAIDs2005

    • Author(s)
      Naohito Ohno
    • Journal Title

      Toxicology of 1→3-Beta-Glucans

      Pages: 143-159

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Particulate and soluble β-glucans from Candida albicans modulate cytokine release from human leukocytes2005

    • Author(s)
      Ken-ichi Ishibashi, Yukari Nakagawa, Naohito Ohno, Toshimi Murai
    • Journal Title

      Toxicology of 1→3-Beta-Glucans

      Pages: 161-177

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Journal Article] Effect of Nitric Oxide on β-Glucan/Indomethacin-Induced Septic Shock2005

    • Author(s)
      Sachiko Nameda, Maki Saito, Noriko N, Miura, Yoshiyuki Adachi, Naohito Ohno
    • Journal Title

      Biol.Pharm.Bull. 28

      Pages: 1254-1258

    • Related Report
      2005 Annual Research Report
  • [Book] Toxicology of 1 → 3・Beta-Glucans2006

    • Author(s)
      Ken-ichi Ishibashi, Yukari Nakagawa, Naohito Ohno, Toshimi Murai
    • Total Pages
      17
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Toxicology of 1 → 3・Beta-Glucans2005

    • Author(s)
      Yoshiyuki Adachi
    • Total Pages
      14
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Toxicology of 1 → 3・Beta-Glucans2005

    • Author(s)
      Noriko N. Miura
    • Total Pages
      18
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary
  • [Book] Toxicology of 1 → 3・Beta-Glucans2005

    • Author(s)
      Naohito Ohno
    • Total Pages
      17
    • Publisher
      CRC Press
    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2005 Final Research Report Summary

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Published: 2003-04-01   Modified: 2016-04-21  

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