Fundamental study for integrated understanding of the mechanism of DILI and its prediction
| Project/Area Number |
26460190
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Multi-year Fund |
|---|
| Section | 一般 |
|---|
| Research Field |
Medical pharmacy
|
|---|
| Research Institution | Chiba University |
|---|
Principal Investigator |
Sekine Shuichi 千葉大学, 大学院薬学研究院, 講師 (70401007)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
伊藤 晃成 千葉大学, 大学院薬学研究院, 教授 (30323405)
|
|---|
| Project Period (FY) |
2014-04-01 – 2017-03-31
|
| Project Status |
Completed (Fiscal Year 2016)
|
| Budget Amount *help |
¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2015: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2014: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
|
|---|
| Keywords | 薬剤性肝障害 / ミトコンドリア / 薬物代謝酵素 / 胆汁うっ滞 / BSEP / 活性代謝物 / 胆汁鬱滞 / 薬剤反応性 / 薬学 |
|---|
| Outline of Final Research Achievements |
In this research, we tried to elucidate the mechanism of drug-induced liver injury (DILI) onset in humans in order to improve the predictability of DILI risk at the development stage of pharmaceuticals.
In many drugs which have high risk for fulminant hepatitis (eg, benzbromarone (BBR)), mitochondrial permeability transition (MPT) due to the production of highly toxic metabolites in the liver was observed. Moreover, in mice lacking cyclophilin D which controls MPT pore opening, BBR induced DILI was successfully suppressed. In addition, we succeeded in constructing a system that can conveniently evaluate the toxic potential in mitochondria of metabolites. These results are expected to contribute to the production of safe medicines.
|
Report
(4 results)
Research Products
(67 results)
-
-
-
-
-
-
-
-
-
-
[Journal Article] Mitochondrial iron accumulation exacerbates hepatic toxicity caused by hepatitis C virus core protein2015
Author(s)
Sekine S, Ito K, Watanabe H, Nakano T, Moriya K, Shintani Y, Fujie H, Tsutsumi T, Miyoshi H, Fujinaga H, Shinzawa S, Koike K, Horie T.
-
Journal Title
Toxicol Appl Pharmacol
Volume: 282
Issue: 3
Pages: 237-243
DOI
Related Report
Peer Reviewed / Open Access
-
-
-
-
-
[Presentation] Mechanism based integrated assay systems for the prediction of drug induced liver injury2016
Author(s)
Shuichi Sekine, Moemi Kawaguchi, Takumi Nukaga, Takeshi Susukida, Akinori Takemura, Cong Liu, Morihiko Hirota, Shiho Ooeda, Akiko Tamura, Nana Kuwata, Hirokazu Kouzuki, Kousei Ito
Organizer
第31回日本薬物動態学会年会
Place of Presentation
松本
Year and Date
2016-10-13
Related Report
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
