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PROPOSAL FOR NOVEL BIO-MARKERS TO EVALUATE THE ANTIDOTE OF ACETAMINOPHEN POISONING

Research Project

Project/Area Number 21659417
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeSingle-year Grants
Research Field Emergency medicine
Research InstitutionKitasato University

Principal Investigator

FUKUMOTO Mariko  北里大学, 薬学部, 准教授 (40137914)

Project Period (FY) 2009 – 2011
Project Status Completed (Fiscal Year 2011)
Budget Amount *help
¥3,210,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥210,000)
Fiscal Year 2011: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2010: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2009: ¥1,700,000 (Direct Cost: ¥1,700,000)
Keywords急性中毒学 / 酸化ストレスマーカー / アセトアミノフェン中毒 / 8-OHdG / MDA / 酸化ストレスーカー / 8-hydroxy deoxyguanosine / N-アセチルシステイン / グルタチオン / マロンジアルデヒド
Research Abstract

Acetaminophen(APAP) is rapidly absorbed from gastrointestinal tract, and approximately 4% of any ingested amount is metabolized by hepatic cytochrome P450 mixed function oxidase system to an active intermediate metabolite that is thought to produce hepatotoxicity. This metabolite, N-acetyl p-benzoquinone mine(NAPQI), is normally detoxified by conjugation with glutathione and excreted by the urine. After an overdose, when glutathione is rapidly used and the store drop to less than 30% of normal, the unconjugated toxic metabolite may bind covalently to various hepatocellular macromolecules producing necrosis.
To propose the novel biomarker for efficacy of antidote in acetaminophen poisoning, we have evaluated some markers such as total antioxidant power(TAP), 8-hydroxy deoxyguanosine(8-OH-dG) and GSH in RBC and also developed a sensitive HPLC method for measuring malonedialdehyde(MDA) in urine and serum.

Report

(4 results)
  • 2011 Annual Research Report   Final Research Report ( PDF )
  • 2010 Annual Research Report
  • 2009 Annual Research Report
  • Research Products

    (19 results)

All 2011 2010 2009

All Journal Article (12 results) Presentation (6 results) Book (1 results)

  • [Journal Article] N-Acetylsysteine(NAC)によるglutathione補給効果の検証2011

    • Author(s)
      吉村久仁子, 福本真理子, 中原大貴, 山口麻美, 市村萠, 上条吉人, 相馬一亥
    • Journal Title

      中毒研究

      Volume: 24(4) Pages: 336-336

    • Related Report
      2011 Final Research Report
  • [Journal Article] 中毒物質情報の収集・評価・提供2011

    • Author(s)
      福本真理子
    • Journal Title

      月刊薬事

      Volume: 53(6) Pages: 803-806

    • Related Report
      2011 Annual Research Report
  • [Journal Article] N-Acetylcysteine (NAC)によるglutathion (GSH)補給効果の検証2011

    • Author(s)
      吉村久仁子
    • Journal Title

      中毒研究

      Volume: 24 Pages: 336-336

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Acetaminophen蛋白付加物(AP-adducts)の最適な測定タイミングはいつか2011

    • Author(s)
      山口麻美
    • Journal Title

      中毒研究

      Volume: 24 Pages: 335-336

    • Related Report
      2011 Annual Research Report
  • [Journal Article] Acetaminophen蛋白付加物(AP-adducts)は肝内glutathioneの枯渇を反映しているか2010

    • Author(s)
      山口麻美、市村萌, 福本真理子, 吉村久仁子, 上條吉人, 相馬一亥
    • Journal Title

      中毒研究

      Volume: 23(4) Pages: 361-361

    • Related Report
      2011 Final Research Report
  • [Journal Article] Rumack & Matthewのノモグラムの限界、Pros & Cons :アセトアミノフェン中毒の治療にノモグラムは有用か2010

    • Author(s)
      福本真理子
    • Journal Title

      中毒研究

      Volume: 23(2) Pages: 111-115

    • Related Report
      2011 Final Research Report
  • [Journal Article] 臨床中毒分析におけるパラダイムシフト2010

    • Author(s)
      福本真理子
    • Journal Title

      中毒研究

      Volume: 23 Pages: 256-259

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Acetaminophen蛋白付加物(AP-adducts)は日本人中毒症例においても重症度の指標となりうるか2010

    • Author(s)
      市村萌
    • Journal Title

      中毒研究

      Volume: 23 Pages: 362-362

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Rumack &Matthewのノモグラムの限界2010

    • Author(s)
      福本真理子
    • Journal Title

      中毒研究

      Volume: 23 Pages: 111-115

    • Related Report
      2010 Annual Research Report
  • [Journal Article] Acetaminophenの肝毒性に対する新規バイオマーカーの検討2009

    • Author(s)
      友田吉則
    • Journal Title

      中毒研究 22

      Pages: 380-380

    • Related Report
      2009 Annual Research Report
  • [Journal Article] Acetaminophen蛋白付加物(AP-adaucts)の日常的臨床分析のための検討2009

    • Author(s)
      市村萌
    • Journal Title

      中毒研究 22

      Pages: 379-380

    • Related Report
      2009 Annual Research Report
  • [Journal Article] 急性中毒の予後推定2009

    • Author(s)
      白川洋一
    • Journal Title

      中毒研究 22

      Pages: 364-365

    • Related Report
      2009 Annual Research Report
  • [Presentation] Acetaminophen蛋白付加物(AP-adducts)の最適な測定タイミングはいつか2011

    • Author(s)
      友田吉則、福本真理子、市村萠、矢後和夫、吉村久仁子、相馬一亥
    • Organizer
      第33回日本中毒学会総会・学術集会
    • Place of Presentation
      大垣
    • Year and Date
      2011-07-30
    • Related Report
      2011 Final Research Report
  • [Presentation] Acetaminophen蛋白付加物(AP-adducts)の最適な測定タイミングはいつか2011

    • Author(s)
      山口麻美
    • Organizer
      日本中毒学会
    • Place of Presentation
      大垣
    • Year and Date
      2011-07-30
    • Related Report
      2011 Annual Research Report
  • [Presentation] Acetaminophen蛋白付加物(AP-adducts)は日本人中毒症例においても重症度の指標となりうるか2010

    • Author(s)
      市村萌, 福本真理子, 吉村久仁子, 上条吉人, 相馬一亥, 白川洋一, 吉岡敏治
    • Organizer
      第32回日本中毒学会総会
    • Place of Presentation
      岡山
    • Year and Date
      2010-07-24
    • Related Report
      2011 Final Research Report
  • [Presentation] Acetaminophen蛋白付加物(AP-adducts)は肝内glutathioneの枯渇を反映しているか2010

    • Author(s)
      山口麻美
    • Organizer
      日本中毒学会
    • Place of Presentation
      倉敷
    • Year and Date
      2010-07-24
    • Related Report
      2010 Annual Research Report
  • [Presentation] Acetaminophenの肝毒性に対する新規バイオマーカーの検討2009

    • Author(s)
      友田吉則、福本真理子、市村萠、矢後和夫、吉村久仁子、相馬一亥
    • Organizer
      第31回日本中毒学会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-25
    • Related Report
      2011 Final Research Report
  • [Presentation] アセトアミノフェン中毒のトリアージおよび治療方針決定にノムグラムは有用か2009

    • Author(s)
      福本真理子
    • Organizer
      日本中毒学会
    • Place of Presentation
      東京
    • Year and Date
      2009-07-25
    • Related Report
      2009 Annual Research Report
  • [Book] アセトアミノフェン中毒の重症度指標、薬剤師のための救急救命時のスキル & 薬ハンドブック-その知識が命を救う-2010

    • Author(s)
      福本真理子、佐藤博
    • Publisher
      医薬ジャーナル社
    • Related Report
      2011 Final Research Report

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Published: 2009-04-01   Modified: 2016-04-21  

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