Roles of NPC1 in development of drug-induced liver injury.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26460629
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Applied pharmacology
• Research Institution: Kumamoto University
• Principal Investigator: Ishitsuka Yoichi 熊本大学, 大学院生命科学研究部(薬), 准教授 (70423655)
• Co-Investigator(Renkei-kenkyūsha): IRIE Tetsumi 熊本大学, 生命科学研究部, 教授 (60150546)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 薬剤性肝障害 / アセトアミノフェン / NPC1 / 医薬品有害反応

Outline of Final Research Achievements

This study was conducted to evaluate the roles of Npc1 gene in the development of acetaminophen (APAP)-induced liver injury in mice. We observed that Npc1 null mice were protected from hepatotoxicity induced by APAP overdose compared with wild-type mice. Although significant difference was mot observed in CYP2E1 expression and toxic metabolite production in liver, the key mediators in APAP hepatotoxicity, such as JNK phosphorylation, nitrotyrosine formation and DNA fragmentation were significantly attenuated in Npc1 null mice.
These results suggest that Npc1, at least in part, play a important role in the development of APAP-induced liver injury.

Free Research Field

応用薬理学、医療薬学