Hepatotoxicity induced by metabolic activation of drugs in three-dimensional hepatocyte cultures
| Project/Area Number |
24790111
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Drug development chemistry
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| Research Institution | Hiroshima University |
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Principal Investigator |
SANOH SEIGO 広島大学, 医歯薬保健学研究院(薬), 助教 (00552267)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Project Status |
Completed (Fiscal Year 2013)
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| Budget Amount *help |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2013: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 薬学 / 薬物代謝 / 肝細胞 / 3次元培養 / 肝毒性 / 代謝的活性化 |
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| Research Abstract |
Formation of the reactive metabolites of drugs by drug-metabolizing enzymes expressed in the liver could result in the hepatotoxicity. It is necessary to develop the methods for prediction of hepatotoxicity in drug develpment. In this study, the hepatocytes were seeded to the micro-space cell culture plate to construct the 3-dimensional culture (spheroid) which is expected to mimic the liver. We could confirm hepatotoxicity of acetaminophen by metabolic activation through cytochrome P450 in spheroids. It would be possible to predict the drug induced hepatotoxicy via metabolic activation qualitatively at least by using this approach.
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Report
(3 results)
Research Products
(19 results)
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[Journal Article] Predictability of metabolism of ibuprofen and naproxen using chimeric mice with human hepatocytes2012
Author(s)
Sanoh S, Horiguchi A, Sugihara K, Kotake Y, Tayama Y, Uramaru N, Ohshita H, Tateno C, Horie T, Kitamura S, Ohta S
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Journal Title
Drug Metab Dispos
Volume: 40(12)
Issue: 12
Pages: 2267-72
DOI
Related Report
Peer Reviewed
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