Analysis of idiosyncratic drug toxicity using mitochondria isolated from an animal model of metabolic syndrome
| Project/Area Number |
26670084
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Teikyo Heisei University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
HAMADA Kazuma 帝京平成大学, 薬学部, 講師 (90596884)
NAKANO Takafumi 帝京平成大学, 薬学部, 助教 (40720793)
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| Project Period (FY) |
2014-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Keywords | 肝障害 / 生活習慣病 / ミトコンドリア毒性 / 医薬品 / 毒性予測 / ミトコンドリア / 医薬品毒性 / MPT / 酸素消費 / 糖尿病 / 薬物感受性 / 特異体質性薬物毒性 |
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| Outline of Final Research Achievements |
Although it has been suggested that underlying disease could be a nongenetic risk factor for idiosyncratic drug-induced liver injury (DILI), little is known about the mechanisms that determine the increased sensitivity to DILI. In addition to patient risk factors, drug related risk factors including mitochondrial toxicity have also been proposed to explain the complex mechanisms of DILI. The objective of this study was to determine whether the fatty liver in type 2 diabetes (T2D) is more susceptible to mitochondrial permeability transition (MPT), characterized by swelling and membrane depolarization that are associated with DILI. Our result showed that T2D enhanced susceptibility to drug-induced MPT. We also demonstrated that the liver mitochondria isolated from T2D mice had increased oxygen consumption stimulated by an uncoupler compared to normal liver mitochondria (NLM). It might be a useful tool to predict DILI in T2D patients, because its sensitivity to drug is different from NLM.
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Report
(3 results)
Research Products
(11 results)
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[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.
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Journal Title
Toxicol Appl Pharmacol
Volume: 282
Issue: 3
Pages: 237-243
DOI
Related Report
Peer Reviewed / Open Access
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