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KMID : 0370220150590050201
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Yakhak Hoeji
2015 Volume.59 No. 5 p.201 ~ p.206
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The Optimization of Method for Prediction of Drug-Induced Liver Injury Using HepG2 Cells Cultured with Human Liver Microsomes
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최종민:Choi Jong-Min
전장수:Jeon Jang-Su/김상겸:Kim Sang-Kyum/전장수:Jeon Jang-Su/김상겸:Kim Sang-Kyum
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Abstract
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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 The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system.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 ethapyrilene,
a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system.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 druginduced hepatotoxicity.
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KEYWORD
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drug toxicity, cytochrome P450, microsomes, in vitro assay, optimization
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