Research on Drug-Induced Liver Injury Associated with MetabolicActivation by CYP
| Project/Area Number |
22390020
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Drug development chemistry
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| Research Institution | The University of Tokyo |
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Principal Investigator |
HISAKA Akihiro 東京大学, 医学部附属病院, 特任准教授 (80420206)
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| Co-Investigator(Kenkyū-buntansha) |
YAMAMOTO Takehito 東京大学, 医学部附属病院, 助教 (00376469)
ITO Kousei 東京大学, 医学部附属病院, 助教 (30323405)
鈴木 洋史 東京大学, 医学部附属病院, 教授 (80206523)
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| Co-Investigator(Renkei-kenkyūsha) |
HONMA Masashi 東京大学, 医学部附属病院, 助教 (60401072)
IKEBUCHI Yuki 東京大学, 医学部附属病院, 助教 (20645725)
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| Project Period (FY) |
2010 – 2012
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| Project Status |
Completed (Fiscal Year 2012)
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| Budget Amount *help |
¥10,530,000 (Direct Cost: ¥8,100,000、Indirect Cost: ¥2,430,000)
Fiscal Year 2012: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2011: ¥3,120,000 (Direct Cost: ¥2,400,000、Indirect Cost: ¥720,000)
Fiscal Year 2010: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
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| Keywords | 医薬品化学 / 薬剤性肝障害 / 炎症性サイトカイン / 療・福祉 / トランスレーショナルリサーチ / 蛋白質 / 薬剤反応性 / 臨床 / 医療・福祉 |
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| Research Abstract |
In our previous study, the decrease of glutathione and the increase of four inflammatory cytokines in blood were identified as nongenetic risk factors of drug induced liver injury (DILI) in patients. In this study, cell toxicity was evaluated using rat primary isolated hepatocytes in the presence and the absence of these risk factors for 223 drugs, and it was revealed that the ratio correlated well with the observed risk of DILI in human. This method was superior to the standard method based on the amount of protein adducts, and would be useful for new drug development in the near future.
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Report
(4 results)
Research Products
(18 results)
