Molecular mechanisms of drug-induced liver injury based on metabolic liver disease

Research Project

Project/Area Number	17KK0158
Research Category	Fund for the Promotion of Joint International Research (Fostering Joint International Research)
Allocation Type	Multi-year Fund
Research Field	Veterinary medical science
Research Institution	Osaka Prefecture University
Principal Investigator	Izawa Takeshi 大阪府立大学, 生命環境科学研究科, 准教授 (20580369)
Project Period (FY)	2017 – 2019
Project Status	Completed (Fiscal Year 2019)
Budget Amount *help	¥13,910,000 (Direct Cost: ¥10,700,000、Indirect Cost: ¥3,210,000)
Keywords	脂肪肝 / 代謝性肝疾患 / 薬剤性肝傷害 / メタボリックシンドローム / 肝疾患 / 薬剤性肝障害 / メタボリック症候群 / マウス / アセトアミノフェン / 薬物代謝 / 毒性病理学
Outline of Final Research Achievements	The present study investigated the change in susceptibility to acetaminophen-induced liver injury in a murine model of nonalcoholic fatty liver disease (NAFLD; DIO-NTac mouse), developing diet-induced fatty liver with obesity and altered glucose tolerance. Liver injury induced by an acetaminophen administration was reduced in DIO-NTac mice compered with control mice, suggesting a decreased susceptibility to acetaminophen hepatotoxicity in this mouse model. The decreased susceptibility was shown to be associated with alteration of xenobiotic enzymes by fatty liver.
Academic Significance and Societal Importance of the Research Achievements	本研究では，近年問題視される非アルコール性脂肪性肝疾患（NAFLD）に合併する薬剤性肝傷害のメカニズム解明を試みた。国内のNAFLD患者は成人の20～30%と考えられており，また患者の多くは医薬品を継続的に服用する必要があることから，本研究で得られたデータが，NAFLD患者に対する治療や医薬品開発の一助となることが期待される。