Comparison of in vitro models for drug-induced liver injury assessment
10.12729/jbtr.2024.25.2.53
- Author:
Nam-Ju KIM
1
;
Ji-Hyun BANG
;
Hee YI
;
Hyun-Ok KU
;
Joong-Sun KIM
;
Ji-Yeon KIM
;
Byung-Suk JEON
Author Information
1. Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea
- Publication Type:Original Article
- From:
Journal of Biomedical and Translational Research
2024;25(2):53-67
- CountryRepublic of Korea
- Language:English
-
Abstract:
Drug-induced liver injury (DILI) is considered to be a significant cause of drug wastage. Tomitigate clinical DILI risks, assessing drugs using human liver models is crucial since animal studies may fall short due to species-specific liver pathway variations. Cell-based preclinical hepatotoxicity testing is often pertinent. In the present study, cells from a human liver cancer line (HepG2 and HepaRG) were cultured in both formats of 2D and 3D spheroids to explore their responses to drugs. Liver-specific marker expressions across cell lines and culture formats were also examined to assess disparities in DILI marker expressions. After treating each cell with the drugs, cytotoxicity and liver injury markers aspartate aminotransferase and alanine aminotransferase were increased. In addition, liver specific markers albumin and urea decreased in a drug concentration-dependent manner. These findings were consistent with drug sensitivity. Additionally, mRNA expression levels of cytochrome P450 enzymes (CYPs) involved in hepatocellular drug metabolism were compared following treatment with enzyme inducers. CYP1A2 and CYP2C9 were not epxressed in HepG2 cells. HepaRG cells exhibited significantly increased expression of CYP1A2, 2C9, and 3A4 post-treatment. No-tably, enzyme expression was notably higher in 3D cultures than in 2D cultures. Collectively, these findings suggest that HepaRG cells and 3D cultures hold promise for evaluating DILI during early-stage drug development.
