| Project/Area Number |
23790174
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | The Institute of Physical and Chemical Research (2012)
The University of Tokyo (2011) |
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Principal Investigator |
YOSHIKADO Takashi 独立行政法人理化学研究所, 杉山特別研究室, 研究員 (70535096)
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| Project Period (FY) |
2011 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2011: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 薬物誘発性胆汁うっ滞 / トランスポーター / 薬剤性肝障害 / 胆汁酸依存性胆汁 / 胆汁酸非依存性胆汁 / 胆汁ミセル / 胆汁形成 / 阻害剤 / 発現量の変動 |
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| Research Abstract |
In this study, bile canalicular transporter-mediated mechanisms of drug-induced cholestasis were analyzed. Effects of cholestatic drugs on the bile composition and on the function of transporters were examined by in vivo and in vitro experiments. In the case of ticlopidine, transporter-mediated biliary excretions of its glutathione- conjugated metabolites affected the bililary secretion of phospholipids, which might lead to liver injury. In addition, further studies using sandwich-cultured human hepatocytes were performed to analyze complex mechanisms of drug-induced cholestasis: metabolisms of drugs and changes in expression/localization of transporters.
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