약학회지 (YAKHAK HOEJI)

  • 제59권5호
  • /
  • Pages.201-206
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  • 2015
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  • 0377-9556(pISSN)
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  • 2383-9457(eISSN)
대한약학회 (The Pharmaceutical Society of Korea)
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Human Liver Microsomes과 HepG2 세포를 이용한 약물유래 간독성 평가 방법의 최적화

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

  • 투고 : 2015.04.24
  • 심사 : 2015.07.17
  • 발행 : 2015.10.31
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초록

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 The cytotoxic effect of chlormezanone, a withdrawn drug due to hepatotoxicity in human, was increased by HLM in the presence of the NADPH-generating system. In contrast, the cytotoxic effect of methapyrilene, a withdrawn drug due to hepatotoxicity in rats, was decreased by HLM in the presence of the NADPH-generating system.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.

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참고문헌

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