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2011 Fiscal Year Final Research Report

Analysis of the molecular mechanism of hepatic GSH decrease during drug induced liver injury.

Research Project

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Project/Area Number 22790146
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeSingle-year Grants
Research Field Medical pharmacy
Research InstitutionThe University of Tokyo

Principal Investigator

ITO Kousei  東京大学, 医学部附属病院, 准教授 (30323405)

Project Period (FY) 2010 – 2011
Keywords医療・福祉 / 薬剤反応性 / 薬剤性肝障害 / トランスポーター
Research Abstract

It is known that pretreatment of minimum amount of lipopolysaccharide(LPS) increases the animals to drug-induced liver injury, otherwise they are hardly affected by drug alone. In addition to previously proposed inflammatory cytokines produced by LPS pre-treatment, we have demonstrated that hepatic GSH decrease is an important factor cooperatively aggravates DILI in this LPS model. Moreover, species difference of the mechanism of hepatic GSH decrease after LPS treatment was emerged ; basolateral efflux of GSH was increased in rat, while metabolic pathway was somehow involved in mouse.

  • Research Products

    (9 results)

All 2012 2011 2010 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results) Presentation (6 results) Remarks (1 results)

  • [Journal Article] Sustained intrahepatic glutathione depletion causes proteasomal degradation of multidrug esistance-associated protein 2 in rat liver

    • Author(s)
      Sekine S, Mitsuki K, Ito K, Kugioka S and Horie T
    • Journal Title

      Biochim Biophys Acta

      Volume: 1822 Pages: 980-987

    • Peer Reviewed
  • [Journal Article] Itraconazole-induced cholestasis : involvement of the inhibition of bile canalicular phospholipid translocator MDR3/ABCB4

    • Author(s)
      Yoshikado T, Takada T, Yamamoto T, Yamaji H, Ito K, Santa T, Yokota H, Yatomi Y, Yoshida H, Goto J, Tsuji S and Suzuki H
    • Journal Title

      Mol Pharmacol

      Volume: 79 Pages: 241-250

    • Peer Reviewed
  • [Presentation] Hepatic glutathione decrease and inflammatory cytokines are key factors in lipopolysaccharide pre-administered drug-induced liver injury model2012

    • Author(s)
      Ito K, Ikebuchi Y, Honma M, Kozawa M, Yamamoto T and Suzuki H
    • Organizer
      International Symposium on Past, Present and Future of Molecular Pharmacokinetics(PPF)
    • Place of Presentation
      Integration of Basic Science, Drug Development and Regulation Tokyo, Japan
    • Year and Date
      20120116-18
  • [Presentation] 薬物誘発性肝障害モデル動物における肝臓内グルタチオン量変化の重要性2011

    • Author(s)
      伊藤晃成,池淵祐樹,本間雅,小沢政成,山本武人and鈴木洋史
    • Organizer
      日光シンポジウム
    • Place of Presentation
      日光
    • Year and Date
      20111217-18
  • [Presentation] 酸化ストレス誘発性胆汁うっ滞時におけるMRP2の局在制御機構の解明2011

    • Author(s)
      関根秀一,伊藤晃成and堀江利治
    • Organizer
      第33回生体膜と薬物の相互作用シンポジウム
    • Place of Presentation
      岡山
    • Year and Date
      20111124-25
  • [Presentation] Post-translational regulation of ABC transporters involved in bile flow formation2011

    • Author(s)
      伊藤晃成,関根秀一,堀江利治and鈴木洋史
    • Organizer
      第88回日本生理学会大会第116回日本解剖学会総会・全国学術集会
    • Place of Presentation
      横浜
    • Year and Date
      20110328-30
  • [Presentation] Hepatic glutathione and inflammatory cytokines cooperatively regulate onset of drug-induced liver injury2010

    • Author(s)
      Ikebuchi Y, Ito K, Honma M, Kozawa M, Yamamoto T and Suzuki H
    • Organizer
      第4回次世代を担う若手医療薬科学シンポジウム
    • Place of Presentation
      東京
    • Year and Date
      20101127-28
  • [Presentation] Glutathione decrease is one of key factors for drug-induced liver injury in rats induced by lipopolysaccharide and diclofenac coadministration2010

    • Author(s)
      Ikebuchi Y, Ito K, Honma M, Kozawa M, Yamamoto T and Suzuki H
    • Organizer
      25th JSSX Annual Meeting
    • Place of Presentation
      大宮
    • Year and Date
      20101007-09
  • [Remarks]

    • URL

      http://square.umin.ac.jp/todaiyak/

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Published: 2013-07-31   Modified: 2015-12-15  

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