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Development of Specific Antidotes for CO and CN Poisoning in House Fire

Research Project

Project/Area Number 23659749
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Anesthesiology/Resuscitation studies
Research InstitutionTokai University

Principal Investigator

KAWAGUCHI Akira  東海大学, 医学部, 教授 (30195052)

Co-Investigator(Kenkyū-buntansha) INOKUCHI Sadaki  東海大学, 医学部, 教授 (60160008)
Co-Investigator(Renkei-kenkyūsha) KANO Koji  同志社大学, 理工学部, 教授 (60038031)
Project Period (FY) 2011 – 2012
Project Status Completed (Fiscal Year 2012)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2012: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2011: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
Keywords蘇生学 / 家屋火災 / 有毒ガス / 蘇生 / 外呼吸 / 内呼吸
Research Abstract

There still are numerous victims of premature death from carbon-monoxide (CO) and hydrogen-cyanide (HCN) poisoning in house fire. CO combines tightly to hemoglobin to inhibit outer respiration and CN‐ion (CN‐) interferes intracellular mitochondrial electron transfer cascade to block inner respiration. We collaborate with Doshisha University to develop supramolecular complex of iron porphylin and cyclodextrin dimer as a specific antidote for CO (Hemocyclodextrin: HemoCD) as well as an antidote for CN‐(Imidazolecyclodextrin: ImCD). In this study, we evaluate these antidotes first in vitro and then in vivo in animal experiments to compare their function with traditional antidotes or saline infusion as the control. In in vitro CN‐toxicity studies [1], we found that ImCD reverse the CN‐toxicity in a dose dependent manner; while an equimolar dose of ImCD completely reversed the CN‐toxicity in terms of cytochrome activity and cell viability, hydroxocobalamine (OHCbl) protected only 80% of the cytochrome activity compared with the control cells without CN‐challenge. In in vivo, ImCD pretreatment significantly reduced the incidence of apnea after intra-gastric KCN administration (ImCD 0/9, OHCbl 5/9, Saline 9/9, P

Report

(3 results)
  • 2012 Annual Research Report   Final Research Report ( PDF )
  • 2011 Research-status Report
  • Research Products

    (28 results)

All 2013 2012 2011 Other

All Journal Article (4 results) (of which Peer Reviewed: 4 results) Presentation (22 results) Patent(Industrial Property Rights) (2 results)

  • [Journal Article] Importance of pH in in Vitro assessment of cyanide toxicity2013

    • Author(s)
      Yamagiwa T, Sito T, Inokuchi S, Kawaguchi AT
    • Journal Title

      Tokai J of Exp Clin Med

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Supramolecular ferric porphyrins and a cyclodextrin dimmer as an antidote for cyanide poisoning2013

    • Author(s)
      Yamagiwa T, Kawaguchi AT, Sito T, Inoue S, Morita S, Watanabe K, Kitagishi H, Kano K, Inokuchi S, et al
    • Journal Title

      Human and Experimental Toxicology 2013

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Supramolecular iron porhyrin/cyclo-dextrin dimmer complex that mimics the functions of hemoglobin and methemoglobin2013

    • Author(s)
      Watanabe K, Kitagishi H, Kano K
    • Journal Title

      Angew Chem Int Ed

      Volume: 25 Pages: 1-5

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Journal Article] Modification of a dioxygen carrier, with PEGylated dendrons for extension of circulation time in the bloodstream2012

    • Author(s)
      Karasugi K, Kitagishi H, Kano K
    • Journal Title

      Bioconjugate chem

      Volume: 23 Pages: 2365-2376

    • Related Report
      2012 Final Research Report
    • Peer Reviewed
  • [Presentation] Imidazole Cyclodextrin as a Novel Antidote for Acute Cyanide Poisoning: Comparison with Existing Antidotes2012

    • Organizer
      国際熱傷学会
    • Place of Presentation
      山際,エディンバラ/イギリス
    • Year and Date
      2012-09-10
    • Related Report
      2012 Final Research Report
  • [Presentation] iposome-encapsulated hemoglobin enhances chemotherapy to suppress tumor growth andmetastasis in mice2012

    • Organizer
      ASAIO
    • Place of Presentation
      川口,サンフランシスコ/アメリカ
    • Year and Date
      2012-06-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Liposome-encapsulated hemoglobin is protective immediately prior to reperfusion in 2-hour cerebralischemia model in the rat2012

    • Organizer
      ASAIO
    • Place of Presentation
      川口,サンフランシスコ/アメリカ
    • Year and Date
      2012-06-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Effect of liposome-encapsulated hemoglobin on low-grade cardiopulmonary exercise in the rat2012

    • Organizer
      ASAIO
    • Place of Presentation
      川口,サンフランシスコ/アメリカ
    • Year and Date
      2012-06-16
    • Related Report
      2012 Final Research Report
  • [Presentation] Immidazole cyclodextrin as an antidote for acute cyanide poisoning2012

    • Organizer
      ASAIO
    • Place of Presentation
      川口,サンフランシスコ/アメリカ
    • Year and Date
      2012-06-14
    • Related Report
      2012 Final Research Report
  • [Presentation] Therapeutic use of liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia and reperfusion in the gerbil2012

    • Organizer
      ASAIO
    • Place of Presentation
      川口,サンフランシスコ/アメリカ
    • Year and Date
      2012-06-14
    • Related Report
      2012 Final Research Report
  • [Presentation] 青酸に対するイミダゾール配位超分子鉄ポルフィリン(ImCD)の解毒効果2012

    • Organizer
      日本救急医学会総会
    • Place of Presentation
      山際、京都府/日本
    • Related Report
      2012 Final Research Report
  • [Presentation] 青酸に対するイミダゾール配位超分子鉄ポルフィリン(ImCD)の解毒効果2012

    • Author(s)
      山際武志
    • Organizer
      第40回日本救急医学会総会
    • Place of Presentation
      京都
    • Related Report
      2012 Annual Research Report
  • [Presentation] Imidazole cyclodextrin (ImCD), totally synthetic supramolecular complex as an antidote for cyanide poisoning2011

    • Organizer
      ESAO&IFAO
    • Place of Presentation
      山際,ポルト/ポルトガル
    • Year and Date
      2011-10-09
    • Related Report
      2012 Final Research Report
  • [Presentation] Imidazole Cyclodextrin (ImCD) as an antidote for Cyanide Poisoning: In Vitro and In Vivo Results The International Association of Forensic Toxicologists2011

    • Organizer
      TIAFT
    • Place of Presentation
      山際,サンフランシスコ/アメリカ
    • Year and Date
      2011-09-30
    • Related Report
      2012 Final Research Report
  • [Presentation] In vitroにおけるシアン化合物に対する解毒剤の評価方法の確立2011

    • Organizer
      日本中毒学会総会
    • Place of Presentation
      山際,エディンバラ/イギリス
    • Year and Date
      2011-07-30
    • Related Report
      2012 Final Research Report
  • [Presentation] In vitroにおけるシアン化合物に対する解毒剤の評価方法の確立2011

    • Author(s)
      山際 武志、川口 章、猪口 貞樹 他
    • Organizer
      第33回日本中毒学会総会
    • Place of Presentation
      岐阜 ソフトピアジャパン
    • Related Report
      2011 Research-status Report
  • [Presentation] 急性シアン化合物中毒に対する新たな全合成解毒剤"イミダゾールシクロデキストリン"のin vitroにおける効果2011

    • Author(s)
      山際 武志、川口 章、猪口 貞樹 他
    • Organizer
      第39回日本救急医学会総会
    • Place of Presentation
      東京 京王プラザホテル
    • Related Report
      2011 Research-status Report
  • [Presentation] Imidazole Cyclodextrin (ImCD) as an antidote for Cyanide Poisoning: In Vitro and In Vivo Results2011

    • Author(s)
      Yamagiwa , Kawaguchi , Inokuti , et al
    • Organizer
      The International Association of Forensic Toxicologists (TIAFT)
    • Place of Presentation
      San Francisco, USA Marriott Marquis Hotel
    • Related Report
      2011 Research-status Report
  • [Presentation] Imidazole cyclodextrin (ImCD), totally synthetic supramolecular complex as an antidote for cyanide poisoning.2011

    • Author(s)
      Yamagiwa , Kawaguchi , Inokuti , et al
    • Organizer
      ESAO&IFAO
    • Place of Presentation
      Porto, Portugal, Porto Congress Centre
    • Related Report
      2011 Research-status Report
  • [Presentation] 急性シアン化合物中毒に対する新たな全合成解毒剤"イミダゾールシクロデキストリン"のin vitroにおける効果

    • Place of Presentation
      山際,エディンバラ/イギリス
    • Related Report
      2012 Final Research Report
  • [Presentation] Immidazole cyclodextrin as an antidote for acute cyanide poisoning.

    • Author(s)
      AkiraT Kawaguchi
    • Organizer
      ASAIO
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Therapeutic use of liposome-encapsulated hemoglobin alleviates hearing loss after transient cochlear ischemia and reperfusion in the gerbil.

    • Author(s)
      AkiraT Kawaguchi
    • Organizer
      ASAIO
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Effect of liposome-encapsulated hemoglobin on low-grade cardiopulmonary exercise in the rat.

    • Author(s)
      AkiraT Kawaguchi
    • Organizer
      ASAIO
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Liposome-encapsulated hemoglobin is protective immediately prior to reperfusion in 2-hour cerebral ischemia model in the rat.

    • Author(s)
      AkiraT Kawaguchi
    • Organizer
      ASAIO
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Liposome-encapsulated hemoglobin enhances chemotherapy to suppress tumor growth and metastasis in mice.

    • Author(s)
      AkiraT Kawaguchi
    • Organizer
      ASAIO
    • Place of Presentation
      サンフランシスコ
    • Related Report
      2012 Annual Research Report
  • [Presentation] Imidazole Cyclodextrin as a Novel Antidote for Acute Cyanide Poisoning: Comparison with Existing Antidotes

    • Author(s)
      Takeshi Yamagiwa
    • Organizer
      第16回国際熱傷学会
    • Place of Presentation
      エディンバラ
    • Related Report
      2012 Annual Research Report
  • [Patent(Industrial Property Rights)] 循環補助薬2011

    • Inventor(s)
      川口章、森本克己、金田伸一
    • Industrial Property Rights Holder
      テルモ株式会社
    • Filing Date
      2011-09-15
    • Related Report
      2012 Final Research Report
  • [Patent(Industrial Property Rights)] 循環補助薬2011

    • Inventor(s)
      川口章、森本克己、金田伸一
    • Industrial Property Rights Holder
      テルモ株式会社
    • Filing Date
      2011
    • Related Report
      2011 Research-status Report

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Published: 2011-08-05   Modified: 2019-07-29  

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