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J. Vet. Sci. 2019; 20(1): 34-42  https://doi.org/10.4142/jvs.2019.20.1.34
High-content analysis of in vitro hepatocyte injury induced by various hepatotoxicants
Nga T. T. Tham, So-Ryeon Hwang, Ji-Hyun Bang, Hee Yi, Young-Il Park, Seok-Jin Kang, Hwan-Goo Kang, Yong-Sang Kim, Hyun-Ok Ku*
Toxicological Evaluation Laboratory, Animal and Plant Quarantine Agency, Gimcheon 39660, Korea
Correspondence to: *Tel: +82-54-912-0571; Fax: +82-54-912-0583; E-mail: kuho@korea.kr
Received: August 10, 2018; Revised: October 18, 2018; Accepted: October 18, 2018; Published online: January 31, 2019.
Abstract
In vitro prediction of hepatotoxicity can enhance the performance of non-clinical animal testing for identifying chemical hazards. In this study, we assessed high-content analysis (HCA) using multi-parameter cell-based assays as an in vitro hepatotoxicity testing model using various hepatotoxicants and human hepatocytes such as HepG2 cells and human primary hepatocytes (hPHs). Both hepatocyte types were exposed separately to multiple doses of ten hepatotoxicants associated with liver injury whose mechanisms of action have been described. HCA data were obtained using fluorescence probes for nuclear size (Hoechst), mitochondrial membrane potential (TMRM), cytosolic free calcium (Fluo-4AM), and lipid peroxidation (BODIPY). Cellular alterations were observed in response to all hepatotoxicants tested. The most sensitive parameter was TMRM, with high sensitivity at a low dose, next was BODIPY, followed by Fluo-4AM. HCA data from HepG2 cells and hPHs were generally concordant, although some inconsistencies were noted. Both hepatocyte types showed mild or severe mitochondrial impairment and lipid peroxidation in response to several hepatotoxicants. The results demonstrate that the application of HCA to in vitro hepatotoxicity testing enables more efficient hazard identification, and further, they suggest that certain parameters could serve as sensitive endpoints for predicting the hepatotoxic potential of chemical compounds.
Keywords: High-content analysis, Multi-parameter cell-based assay, HepG2 cell, Human primary hepatocyte, Hepatotoxicity


© 2019 The Korean Society of Veterinary Science.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.