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Investigation of hepatic warfarin metabolism activity in rodenticide-resistant black rats (Rattus rattus)

Research Project

Project/Area Number 16K15034
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Veterinary medical science
Research InstitutionHokkaido University

Principal Investigator

Ishizuka Mayumi  北海道大学, 獣医学研究科, 教授 (50332474)

Co-Investigator(Kenkyū-buntansha) 池中 良徳  北海道大学, 獣医学研究院, 准教授 (40543509)
中山 翔太  北海道大学, 獣医学研究院, 助教 (90647629)
水川 葉月  北海道大学, 獣医学研究院, 助教 (60612661)
Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2017: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2016: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords殺鼠剤 / 抵抗性 / ラット / 殺鼠剤抵抗性 / 薬剤耐性 / ワルファリン / クマネズミ / 薬物代謝 / シトクロムP440 / 野生齧歯類 / クローズドコロニー
Outline of Final Research Achievements

Anti-blood coagulation rodenticides, such as warfarin, have been used all over the world. They inhibit vitamin K epoxide reductase (VKOR), which is necessary for producing several blood clotting factors. This inhibition by rodenticides results in lethal hemorrhage in rodents. However, heavy usage of these agents has led to the appearance of rodenticide-resistant rats. The mutation of the target enzyme of warfarin, VKOR, is considered as major cause for rodenticide resistance in wild rats. However, there have been few studies regarding the hepatic metabolism of warfarin. We investigated warfarin metabolism in resistant rats, and our results showed new mechanism for the rodenticide resistance in wild black rats in Japan.

Report

(3 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • Research Products

    (17 results)

All 2018 2017 2016 Other

All Int'l Joint Research (1 results) Journal Article (4 results) (of which Int'l Joint Research: 2 results,  Peer Reviewed: 4 results,  Open Access: 4 results,  Acknowledgement Compliant: 3 results) Presentation (12 results) (of which Int'l Joint Research: 3 results,  Invited: 3 results)

  • [Int'l Joint Research] カセサート大学(タイ)

    • Related Report
      2016 Research-status Report
  • [Journal Article] Investigation of hepatic warfarin metabolism activity in rodenticide-resistant black rats ( Rattus rattus ) in Tokyo by in situ liver perfusion2018

    • Author(s)
      Kazuki Takeda, Yoshinori Ikenaka, Kazuyuki D.Tanaka, Shouta M.M .Nakayama, Tsutomu Tanikawa, Hazuki Mizukawa, Mayumi Ishizuka
    • Journal Title

      Pesticide Biochemistry and Physiology

      Volume: in press Pages: 42-49

    • DOI

      10.1016/j.pestbp.2018.03.018

    • NAID

      120006636185

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Monitoring lead (Pb) pollution and identifying Pb pollution sources in Japan using stable Pb isotope analysis with kidney of wild rats.2017

    • Author(s)
      Nakata H*, Nakayama SMM*, Oroszlany B, Ikenaka Y, Mizukawa H, Tanaka K, Harunari T, Tanikawa T, Darwish WS, Yohannes YB, Saengtienchai A, Ishizuka M (* Equal contribution).
    • Journal Title

      Int. J. Environ. Res. Public Health

      Volume: in press Issue: 1 Pages: 56-56

    • DOI

      10.3390/ijerph14010056

    • NAID

      120005981457

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Novel revelation of warfarin resistant mechanism in roof rats (Rattus rattus) using pharmacokinetic/pharmacodynamic analysis.2016

    • Author(s)
      Takeda K*, Ikenaka Y*, Tanikawa T, Tanaka KD, Nakayama SMM, Mizukawa H, Ishizuka M (*Equal contribution).
    • Journal Title

      Pestic Biochem Physiol.

      Volume: in press Pages: 1-7

    • DOI

      10.1016/j.pestbp.2016.04.004

    • NAID

      120006360062

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] The African hedgehog (Atelerix albiventris): low phase I and phase II metabolism activities.2016

    • Author(s)
      Saengtienchai A, Ikenaka Y, Bortey-Sam N, Jermnark U, Mizukawa H, Kawai YK, Nakayama SMM, Ishizuka M.
    • Journal Title

      Comp Biochem Physiol C Pharmacol Toxicol.

      Volume: 190 Pages: 38-47

    • DOI

      10.1016/j.cbpc.2016.08.005

    • Related Report
      2016 Research-status Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Presentation] Novel Mechanism of Rodenticide (warfarin) Resistance of Wild Rats in Tokyo ~ Enhanced Pentose Phosphate Pathway Causes Rapid Metabolism of Warfarin ~2018

    • Author(s)
      Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka
    • Organizer
      Society of Toxicology’s 57th Annual Meeting and ToxExpo
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 代謝酵素の動物種差2017

    • Author(s)
      石塚真由美、中山翔太、水川葉月、池中良徳
    • Organizer
      日本薬学会第137年会シンポジウム
    • Place of Presentation
      仙台国際センター、仙台市
    • Year and Date
      2017-03-24
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] In situ肝灌流試験によるワルファリン抵抗性クマネズミでのワルファリン代謝能の解明2017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      第26回環境化学討論会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 肝灌流試験、in vitro酵素活性試験による東京由来ワルファリン抵抗性クマネズミのワルファリン代謝能の解明2017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      第44回日本毒性学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] 東京由来殺鼠剤抵抗性ラットを用いた新規抵抗性獲得機序の解明2017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      第160回日本獣医学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] ペントースリン酸経路の亢進による殺鼠剤代謝能の活性化,第160回日本獣医学会学術年会,2017,2017,0,02017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      第160回日本獣医学会学術年会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Nobel investigation of mechanism of rodenticide resistance2017

    • Author(s)
      Kazuki Takeda、Yoshinori Ikenaka、Tsutomu Tanikawa、Kazuyuki D. Tanaka、Shouta M.M. Nakayama、Hazuki Mizukawa、Mayumi Ishizuka
    • Organizer
      The 5th Sapporo Summer Seminar for One Health (SaSSOH)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Novel Mechanism of Rodenticide (warfarin) Resistance of Wild Rats in Tokyo ~ Enhanced Pentose Phosphate Pathway Causes Rapid Metabolism of Warfarin ~2017

    • Author(s)
      Kazuki Takeda, Yoshinori Ikenaka, Tsutomu Tanikawa, Kazuyuki D. Tanaka, Shouta M.M. Nakayama, Hazuki Mizukawa, Mayumi Ishizuka
    • Organizer
      Society of Toxicology’s 57th Annual Meeting and ToxExpo
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 東京のワルファリン抵抗性ラットの抵抗性獲得機序の解明:ペントースリン酸経路の亢進を通したワルファリン代謝の活性化 Investigation of mechanism of warfarin resistance of wild rats in Tokyo ~ enhanced pentose phosphate pathway causes rapid metabolism of warfarin ~2017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      2017年度生命科学系学会合同年次大会(ConBio2017)
    • Related Report
      2017 Annual Research Report
  • [Presentation] スーパーラットは高NADPH産生能を持つ ~東京の殺鼠剤抵抗性ラットにおける抵抗性獲得機序の解明~2017

    • Author(s)
      武田一貴、池中良徳、田中和之、谷川力、中山翔太、水川葉月、石塚真由美
    • Organizer
      第3回 北大部局間横断シンポジウム
    • Related Report
      2017 Annual Research Report
  • [Presentation] 野生げっ歯類の殺鼠剤の抵抗性メカニズムと非対象動物に対する毒性メカニズム2016

    • Author(s)
      石塚真由美、中山翔太、水川葉月、池中良徳
    • Organizer
      日本哺乳類学会2016年度大会
    • Place of Presentation
      筑波大学、つくば市
    • Year and Date
      2016-09-23
    • Related Report
      2016 Research-status Report
    • Invited
  • [Presentation] 学物質の汚染環境に生きる野生動物の適応戦略2016

    • Author(s)
      石塚真由美、中山翔太、水川葉月、池中良徳
    • Organizer
      日本環境化学会25周年記念講演会
    • Place of Presentation
      発明会館地下ホール、東京都港区
    • Related Report
      2016 Research-status Report
    • Invited

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Published: 2016-04-21   Modified: 2019-03-29  

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