NDLI: The HepaRG cell line, a superior in vitro model to L-02, HepG2 and hiHeps cell lines for assessing drug-induced liver injury

Content Provider	Springer Nature Link
Author	Wu, Yu Geng, Xing chao Wang, Ju feng Miao, Yu fa Lu, Yan li Li, Bo
Copyright Year	2016
Abstract	Drug-induced liver injury (DILI) is a leading cause of discontinuation of new drug approval or withdrawal of marketed medicine based on safety due to organ vulnerability. The aim of this research is to investigate the potential abilities of four different in vitro cell models (L-02, HepG2, HepaRG, and hiHeps cell lines) in assessing marketed drugs labeled with apparently different types of liver injury. A total of 17 drugs with versatile pharmacological profiles were chosen, of which, 14 drugs are recognized as DILI agents and 3 drugs are DILI irrelevant. Preliminary cellular screening assays indicated that the HepaRG cell line had an advantage over other cell lines in predicting drugs associated with DILI in vitro as it had the highest Youden’s index (71.4 %). A multi-parametric screening assay showed that oxidative stress, mitochondrial damage, and disorders of neutral lipid metabolism were changed notably in the HepaRG cell line after DILI-related drugs exposure, accounting for its high sensitivity in comparison with other three cell lines. In addition, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), and malate dehydrogenase (MDH) all correlated with the cytotoxic effects of diclofenac sodium (p < 0.05), buspirone hydrochloride (p < 0.01), and danazol (p < 0.01) in the HepaRG cell line. We conclude that the HepaRG cell line is a superior in vitro cell model to other three cell lines for evaluating drugs with DILI potential.
Starting Page	37
Ending Page	59
Page Count	23
File Format	PDF
ISSN	07422091
Journal	Cell Biology and Toxicology
Volume Number	32
Issue Number	1
e-ISSN	15736822
Language	English
Publisher	Springer Netherlands
Publisher Date	2016-03-30
Publisher Place	Dordrecht
Access Restriction	Subscribed
Subject Keyword	Drug-induced liver injury HepaRG cell line CCK-8 assay High-content screening Malate dehydrogenase Cell Biology Pharmacology/Toxicology Biochemistry
Content Type	Text
Resource Type	Article
Subject	Cell Biology Health, Toxicology and Mutagenesis Toxicology

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