Fundamental study for integrated understanding of the mechanism of DILI and its prediction

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460190
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Medical pharmacy
• Research Institution: Chiba University
• Principal Investigator: Sekine Shuichi 千葉大学, 大学院薬学研究院, 講師 (70401007)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬剤性肝障害 / ミトコンドリア / 薬物代謝酵素 / 胆汁うっ滞 / BSEP

Outline of Final Research Achievements

In this research, we tried to elucidate the mechanism of drug-induced liver injury (DILI) onset in humans in order to improve the predictability of DILI risk at the development stage of pharmaceuticals.
In many drugs which have high risk for fulminant hepatitis (eg, benzbromarone (BBR)), mitochondrial permeability transition (MPT) due to the production of highly toxic metabolites in the liver was observed. Moreover, in mice lacking cyclophilin D which controls MPT pore opening, BBR induced DILI was successfully suppressed. In addition, we succeeded in constructing a system that can conveniently evaluate the toxic potential in mitochondria of metabolites. These results are expected to contribute to the production of safe medicines.

Free Research Field

医薬品安全性学