Establishment of a novel cell-based assay for detection of potential drug-induced liver injury by considering immune- and inflammatory-related factors

2016 Fiscal Year Final Research Report

• Project/Area Number: 15K21057
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pharmacology in pharmacy; Medical pharmacy
• Research Institution: Nagoya University
• Principal Investigator: ODA Shingo 名古屋大学, 医学系研究科, 特任助教 (10725534)
• Research Collaborator: SHIRAI Yuji 名古屋大学, 大学院医学系研究科, 大学院生 ; XU Jieyu 名古屋大学, 大学院医学系研究科, 大学院生
• Project Period (FY): 2015-04-01 – 2017-03-31
• Keywords: 薬物性肝障害 / 薬物代謝 / in vitroアッセイ / 免疫 / 炎症

Outline of Final Research Achievements

This study sought to develop a novel cell-based assay for detecting potential drug-induced liver injury (DILI) by considering drug metabolism as well as immune- and inflammatory-related factors. Human hepatoma HepaRG or HepG2 cells were treated with drugs with different clinical DILI risks. The conditioned media were subsequently used to treat human promyelocytic leukemia HL-60 cells, and the mRNA expression levels were measured. ROC-AUC was calculated to evaluate the predictive performance of each gene mRNA as a marker to assess DILI risk. The expression of IL-8 in HL-60 cells treated with conditioned media from HepaRG cells (HL-60/HepaRG) exhibited the highest ROC-AUC value of 0.758. An integrated score calculated from the levels of S100A9, IL-1beta, and IL-8 more precisely determined the DILI risks than individual gene expression did. The developed cell-based assay using immune-related gene expression would be useful for the detection of potential DILI risks.

Free Research Field

医薬品安全性学