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Evaluation of antihepatotoxic drug effects using chemicals-induced cytotoxicities in primary cultured rat hepatocytes

Research Project

Project/Area Number 61570340
Research Category

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

Allocation TypeSingle-year Grants
Research Field Gastroenterology
Research InstitutionTottori University

Principal Investigator

MURA Tetuo  Division of Chemistry, Institute of Steroid Research Tottori University School o, 化学部門, 講師 (80093631)

Co-Investigator(Kenkyū-buntansha) MIYAKE Mariko  , 医学部附属ステロイド医学研究施設・化学部門, 助手 (20135883)
IKAWA Shiro  , 医学部附属ステロイド医学研究施設・化学部門, 教授 (70032183)
Project Period (FY) 1986 – 1988
Project Status Completed (Fiscal Year 1988)
Budget Amount *help
¥2,000,000 (Direct Cost: ¥2,000,000)
Fiscal Year 1988: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1987: ¥300,000 (Direct Cost: ¥300,000)
Fiscal Year 1986: ¥1,400,000 (Direct Cost: ¥1,400,000)
KeywordsPrimary culture rat hepatocytes / Evaluation of antihepatotoxic drugs / Experimental cholestasis / Bile acid metabolism / グリチルリチンとプロトポルフィリンの薬効評価 / 加齢による核の過酸化脂質付加物 / 四塩化炭素 / Caイオノフォア / 癌原物質 / 不定期DNAと過酸化脂質付加物 / 加齢による肝機能 / 毛細胆管形成とステロイドホルモン / 細胞密度依存性 / カルシウムイオノフォア / 不定期DNA合成 / グリチルリチン / プロトポルフィリン / 実験的肝内胆汁うっ滞モデル / 胆汁酸動態 / 四塩化炭素障害細胞 / 肝特異酵素の漏出 / ガラクトサミン障害細胞
Research Abstract

For primary screening of antihepatotoxic activity of liver-protective drugs, carbon tetrachloride- and calcium ionophore-produced cytotoxicity models utilizing primary cultured rat hepatocytes have been established. The antihepatotoxic effects of the known, such as glycyrrhizine and protoporphyrine, have been evaluated using these methods and thus devised. In the hepatocytes cultured with estradiol-17 -glucuronide (E_2-17G) induced the cholestasis-like state: The decrease of intracellular cAMP, 5'-Nase activity and taurine-conjugated bile acids and the marked increase of sulfated bile acids, especially lithocholic and chenodeoxycholic acid were obsered, while dexamethasone, phenobarbital and ursodeoxycholic acid improved these changes to the control levels.
We also observed that hepatocytes membranes affect the bile acid conjugation on enzyme induction through cell-cell contact. The induction of taurine-conjugated bile acid related to liver specific functions which are high in cells cultured at high cell density, while glycine-conjugated bile acid related to cell growth (such as glucose-6-phosphate dehydrogenase and DNA synthesis) are high at low cell density. These reciprocal regulation of bile acid conjugation may be mediated by a cell surface modulator through effects on gene expression.

Report

(4 results)
  • 1988 Annual Research Report   Final Research Report Summary
  • 1987 Annual Research Report
  • 1986 Annual Research Report
  • Research Products

    (23 results)

All Other

All Publications (23 results)

  • [Publications] 武良哲雄,三宅真里子、猪川嗣朗: 脂質生化学研究. 28. 209-212 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 川崎寛中,武良哲雄,猪川嗣朗: 肝臓. 27. 141-143 (1986)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 武良哲雄,猪川嗣朗: MINOPHAGEN MEDICAL REVIEW. 17. 102-109 (1987)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] TETSUO MURA,;MARIKO MIYAKE,;SHIRO IKAWA,;HIRONAKA KAWASAKI.: J.Biochem.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] TETSUO MURA,;MARIKO MIYAKE,;SHIRO IKAWA,;HIRONAKA KAWASAKI.: J.Pharmacol Exp.Ther.

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 28. 209-212 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 27. 141-143 (1986)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] MINOPHAGEN MEDICAL Review. Supple 17. 102-109 (1987)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] TETUO MURA;MARIKO MIYAKE;SHIRO IKAWA;HIRONAKA KAWASAKI: "Primary culture of rat hepatocytes as a model of intrahepatic cholestasis induced with estradiol-17 -D-glucuronides" J. Biochem.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] TETUO MURA;MARIKO MIYAKE;SHIRO IKAWA;HIRONAKA KAWASAKI: "Evaluation of antihepatotoxic drugs using chemicals-induced cytotoxicities in primary culture of rat hepatocytes" J. Pharmacol Exp Ther.

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      1988 Final Research Report Summary
  • [Publications] 武良哲雄,三宅真里子,猪川嗣朗: 脂質生化学研究. 28. 209-212 (1986)

    • Related Report
      1988 Annual Research Report
  • [Publications] 川崎寛中,武良哲雄,猪川嗣朗: 肝臓. 27. 141-143 (1986)

    • Related Report
      1988 Annual Research Report
  • [Publications] 武良哲雄,猪川嗣朗: MINOPHAGEN MEDICAL REVIEW. 17. 102-109 (1987)

    • Related Report
      1988 Annual Research Report
  • [Publications] TETUO MURA,;MARIKO MIYAKE,;SHIRO IKAWA,;HIRONAKA KAWASAKI: J.Biochem.

    • Related Report
      1988 Annual Research Report
  • [Publications] TETUO MURA,;MARIKO MIYAKE,;SHIRO IKAWA,;HIRONAKA KAWASAKI: J.Pharmacol Exp Ther.

    • Related Report
      1988 Annual Research Report
  • [Publications] 武良哲雄, 三宅真里子, 猪川嗣朗: 脂質生化学研究. 28. 209-212 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] 川崎寛中, 武良哲雄, 猪川嗣朗: 肝臓. 27. 1503-1505 (1986)

    • Related Report
      1987 Annual Research Report
  • [Publications] 武良哲雄, 猪川嗣朗: Minophagen Medical Review. Supple. 17. 102-109 (1987)

    • Related Report
      1987 Annual Research Report
  • [Publications] TETSUO MURA;MARIKO MIYAKE;SHIRO IKAWA;HITONAKA KAWASAKI: J. Lipid. Res.

    • Related Report
      1987 Annual Research Report
  • [Publications] 武良哲雄,三宅真理子,猪川嗣朗: 脂質性化学研究. 28. 209-212 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 川崎寛中,武良哲雄,猪川嗣朗: 肝臓. 27. 1503-1505 (1986)

    • Related Report
      1986 Annual Research Report
  • [Publications] 武良哲雄,猪川嗣朗: 第4回グリチルリチン研究会.

    • Related Report
      1986 Annual Research Report
  • [Publications] TETSUO MURA;MARIKO MIYAKE;SHIRO IKAWA;HIRONAKA KAWASAKI: J.Lipid,Res.

    • Related Report
      1986 Annual Research Report

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Published: 1987-03-31   Modified: 2016-04-21  

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