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Application of biliverdin/bilirubin redox cycle to the novel therapeutic strategy against acute lung injury

Research Project

Project/Area Number 25462450
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Anesthesiology
Research InstitutionOkayama Prefectural University

Principal Investigator

Toru Takahashi  岡山県立大学, 保健福祉学部, 教授 (40252952)

Co-Investigator(Kenkyū-buntansha) MORIMATSU Hiroshi  岡山大学, 医歯薬学総合研究科, 教授 (30379797)
OGINO Tetsuya  岡山県立大学, 保健福祉学部, 教授 (90252949)
SHIMIZU Hiroko  岡山大学, 医学部, 客員研究員 (80423284)
Project Period (FY) 2013-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2014: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Keywords急性肺傷害 / 出血性ショック / ビリベルジン / 炎症 / 酸化ストレス / 酸化的DNA損傷 / 抗炎症作用 / 抗酸化ストレス作用 / 出血性ショック蘇生 / Heme Oxygenase-1 / 一酸化炭素:CO / COヘモグロビン / CO releasing molecule / 周術期管理学 / 8-OHdG / 炎症性サイトカイン
Outline of Final Research Achievements

Hemorrhagic shock and resuscitation (HSR) induces pulmonary inflammation that leads to acute lung injury. Biliverdin, a metabolite of heme catabolism, has been shown to have potent anti-inflammatory, and anti-oxidant effects. We administered biliverdin to a rat model of HSR and examined its effect on HSR-induced lung injury. We found that pre-treatment of HSR rats with biliverdin at a dose of 35 mg/kg markedly ameliorated HSR-induced pulmonary inflammation and oxidative tissue injury in the lung as judged by the histopathological improvement, and the decrease in inflammatory gene expression and DNA oxidative damage without abnormal increase in serum bilirubin levels. We also confirmed that biliverdin administration after HSR had protective effects on lung injury. Our findings suggest that biliverdin has a protective role, at least in part, against HSR-induced lung injury through anti-inflammatory and anti-oxidant mechanisms.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2013 Research-status Report
  • Research Products

    (8 results)

All 2015 2013

All Journal Article (4 results) (of which Peer Reviewed: 3 results,  Open Access: 1 results,  Acknowledgement Compliant: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results,  Invited: 3 results) Book (1 results)

  • [Journal Article] Improvement of heme oxygenase-1-based heme sensor for quantifying free heme in biological samples2015

    • Author(s)
      Junichi Taira, Yukinori Nakashima, Shun Yoshihara, Shinya Koga, Shinji Sueda, Hideyuki Komatsu, Yuichiro Higashimoto, Toru Takahashi, Nohito Tanioka, Hiroko Shimizu, Hiroshi Morimatsu, Hiroshi Sakamoto
    • Journal Title

      Analytical Biochemistry

      Volume: 489 Pages: 50-52

    • DOI

      10.1016/j.ab.2015.08.004

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] 一酸化炭素(CO)産生酵素:ヘムオキシゲナーゼ-1が急性臓器障害において果たす役割.2015

    • Author(s)
      高橋 徹
    • Journal Title

      安定同位体と生体ガス

      Volume: 7 Pages: 42-48

    • NAID

      40020727598

    • Related Report
      2015 Annual Research Report
  • [Journal Article] Morita K: Inhalation of carbon monoxide following resuscitation ameliorates hemorrhagic shock-induced lung injury.2013

    • Author(s)
      Kawanishi S
    • Journal Title

      Mol Med Report

      Volume: 7 Issue: 1 Pages: 3-10

    • DOI

      10.3892/mmr.2012.1173

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Journal Article] Effects of Biliverdin Administration on Acute Lung Injury Induced by Hemorrhagic Shock and Resuscitation in Rats2013

    • Author(s)
      Kosaka J, Morimatsu H, Takahashi T, Shimizu H, Kawanishi S, Omori E, Endo Y, Tamaki N, Morita M, Morita K.
    • Journal Title

      PLoS One

      Volume: 8 Issue: 5 Pages: e63606-e63606

    • DOI

      10.1371/journal.pone.0063606

    • NAID

      120005359106

    • Related Report
      2013 Research-status Report
    • Peer Reviewed
  • [Presentation] Protective role of ulinastatin on lung injury and inflammation induced by hemorrhagic shock.2015

    • Author(s)
      Toru Takahashi
    • Organizer
      The 18th International Symposium on Molecular Medicine
    • Place of Presentation
      Athens, Greece
    • Year and Date
      2015-10-10
    • Related Report
      2015 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] 活性酸素の関与とその制御―抗酸化ストレス蛋白HO-1システムの臨床応用への可能性. シンポジウム:肺傷害発症と重症化のメカニズム―臨床応用への可能性―2015

    • Author(s)
      高橋 徹
    • Organizer
      日本麻酔科学会・第62回学術集会
    • Place of Presentation
      神戸ポートピアホテル
    • Year and Date
      2015-05-29
    • Related Report
      2015 Annual Research Report
    • Invited
  • [Presentation] Protective role of heme oxygenase-1/CO system in hemorrhagic shock-induced acute lung injury2013

    • Author(s)
      Toru Takahashi, Susumu Kawanishi, Jyunko Kosaka, Hiroko Shimizu, Hiroshi Morimatsu
    • Organizer
      16th International Symposium on Molecular Medicine
    • Place of Presentation
      Hersonissos, Crete, Greece
    • Related Report
      2013 Research-status Report
    • Invited
  • [Book] エンドトキシン・自然免疫研究18 自然免疫における生体防御の多様性2015

    • Author(s)
      高橋 徹
    • Total Pages
      100
    • Publisher
      医学図書出版株式会社
    • Related Report
      2015 Annual Research Report

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Published: 2014-07-25   Modified: 2019-07-29  

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