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http://dx.doi.org/10.17480/psk.2015.59.5.201

The Optimization of Method for Prediction of Drug-Induced Liver Injury Using HepG2 Cells Cultured with Human Liver Microsomes  

Choi, Jong Min (College of Pharmacy, Chungnam National University)
Jeon, Jang Su (College of Pharmacy, Chungnam National University)
Kim, Sang Kyum (College of Pharmacy, Chungnam National University)
Publication Information
YAKHAK HOEJI / v.59, no.5, 2015 , pp. 201-206 More about this Journal
Abstract
The aim of the present study was to optimize in vitro method for the prediction of drug-induced liver injury using human liver microsomes (HLM). Cytotoxicity test of cyclophosphamide and acetaminophen in HepG2 cells cultured with HLM showed that the newly established condition using 0.375 mg/ml HLM for 24 hr incubation was comparable or more sensitive than the previously established condition using 0.75 mg/ml HLM for 12 hr incubation. Although the cytotoxic effect of troglitazone was completely attenuated by 0.75 mg/ml HLM, it was augmented by 0.375 mg/ml HLM in the presence of the NADPH-generating system. The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system. The present study suggests that the optimized in vitro method using HLM can be useful for the prediction of drug-induced hepatotoxicity.
Keywords
drug toxicity; cytochrome P450; microsomes; in vitro assay; optimization;
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