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

2019 Fiscal Year Final Research Report

• 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
• Keywords: 脂肪肝 / 代謝性肝疾患 / 薬剤性肝傷害

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.

Free Research Field

毒性病理学

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。