2012 Fiscal Year Final Research Report

Analyses of transporter-mediated mechanisms of drug-induced cholestasis

Research Project

Project/Area Number	23790174
Research Category	Grant-in-Aid for Young Scientists (B)
Allocation Type	Multi-year Fund
Research Field	Medical pharmacy
Research Institution	The Institute of Physical and Chemical Research (2012) The University of Tokyo (2011)
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)
Project Period (FY)	2011 – 2012
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
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.

(4 results)