• Search Research Projects
  • Search Researchers
  • How to Use
  1. Back to previous page

In vitro assessment of susceptibility to toxic drug metabolites

Research Project

Project/Area Number 62570309
Research Category

Grant-in-Aid for General Scientific Research (C)

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionChiba University

Principal Investigator

NOMURA Fumio  Ist Dept. of Med, Chiba Univ. Hospital, 医学部, 助手 (80164739)

Co-Investigator(Kenkyū-buntansha) 田辺 雄一  千葉大学, 医学部・第1内科, 医員
Project Period (FY) 1987 – 1989
Project Status Completed (Fiscal Year 1989)
Budget Amount *help
¥1,900,000 (Direct Cost: ¥1,900,000)
Fiscal Year 1989: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1988: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 1987: ¥1,100,000 (Direct Cost: ¥1,100,000)
KeywordsDrug-induced liver injury / peripheral blood mononuclear cells / Malotilate / hepatic microosmes / 末梢血単核球 / 肝ミクロソ-ム / ハローセン / マロチレート / 薬物性肝障害 / 肝ミクロソーム / アセトアミノフェン
Research Abstract

We made an in vitro assessment of susceptibility to drug metabolites with malotilate as substrate. Peripheral-blood mononulcear cells(PBMCs) were incubated with malotilate(0.12mM) in the presence of the NADPH-generating system and hepatic microsomes(O.025mg protein/ml). Cytotoxicity of malotilate to PBMCs was assessed by trypan blue dye exclusion and LDH release to the culture media, being found to be enhanced by the addition of the NADPH-generating system. The result indicated a significant role of the metabolites in toxicity. More interestingly, the cytotoxicity was remarkably greater in patients with malotilate-induced liver injury than in controls. This in vitro system may be useful in predicting potential toxicity of drugs for selected patients.

Report

(4 results)
  • 1989 Annual Research Report   Final Research Report Summary
  • 1988 Annual Research Report
  • 1987 Annual Research Report
  • Research Products

    (16 results)

All Other

All Publications (16 results)

  • [Publications] 野村文夫 他: "肝疾患における薬物動態" 医学のあゆみ. 145. 656-658 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 野村文夫 他: "薬物活性化反応を利用した薬剤性肝障害in vitro診断の試み" 医学のあゆみ. 150. 565-566 (1989)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats" Anesth Analg.67. 448-452 (1988)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets-A preliminary study" Journal of Hepatology.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "Clinical pharmacokinetics in patients with liver disease" IGAKUNO AYUMI 145:656-658, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "In vitro assessment of susceptibility to toxic drug metabolites" IGAKUNO AYUMI 150:565-566, 1989.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats." Anesth, Analg.67:448-452, 1988.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] Fumio Nomura et al.: "Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets- A preliminary study." Journal of Hepatology.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1989 Final Research Report Summary
  • [Publications] 野村文夫他: "薬物活性化反応を利用した薬剤性肝障害in vitro診断の試み" 医学のあゆみ. 150. 565-566 (1989)

    • Related Report
      1989 Annual Research Report
  • [Publications] 野村文夫他: "肝疾患における薬物動態" 医学のあゆみ. 145. 656-658 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Fumio Nomura et al.: "Halothane hepatotoxicity and reductive metabolism of halothane in acute experimental liver injury in rats" Anesth.Analg. 67. 448-452 (1988)

    • Related Report
      1989 Annual Research Report
  • [Publications] Fumio Nomura et al.: "Detection of malotilate toxicity in vitro with peripheral blood mononuclear cells as targets- A preliminary study" Journal of Hepatology.

    • Related Report
      1989 Annual Research Report
  • [Publications] Fumio,Nomura;et al: Anesth Analy. 67. 448-452 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 野村文夫 他: 医学のあゆみ. 145. 656-658 (1988)

    • Related Report
      1988 Annual Research Report
  • [Publications] 野村文夫 他: 日本消化器病学会誌. 84. 2129 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] Nomura,F. et al: Anesthesia and Analgesia. (1988)

    • Related Report
      1987 Annual Research Report

URL: 

Published: 1987-04-01   Modified: 2016-04-21  

Information User Guide FAQ News Terms of Use Attribution of KAKENHI

Powered by NII kakenhi