| Project/Area Number |
20592133
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Emergency medicine
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| Research Institution | National Research Institute of Police Science |
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Principal Investigator |
SAKURADA Koichi 科学警察研究所, 法科学第一部, 室長 (10334228)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2010: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000)
Fiscal Year 2009: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 神経ガス / オキシム / パム / 2-PAM / 4-PAO / BBB / LC-MS/MS / LC-MS / MS / コリンオキシダーゼ / チトクロームCオキシダーゼ / ミトコンドリア / 電子伝達系 |
|---|
| Research Abstract |
A liquid chromatography-tandem mass spectrometry(LC-MS/MS) method was validated and applied to the in vitro determination of novel PAM-type oximes, which can penetrate the blood-brain barrier(BBB) and reactivate acetylcholinesterase(AChE) inhibited by alkylphosphonate in various organs. It was indicated that the LC-MS/MS method could be a reliable method with high precision and accuracy for quantification of PAM-type oximes in various biological samples. On the other hand, although the oximes are potential antidotes to poisonings that inhibit AChE, but they are also toxic. To investigate the mechanism of their toxicity, the effects of oximes on the enzymes choline oxidase(ChOD) and cytochrome c oxidase(CyCOD) of the respiratory chain in mitochondria were examined. The results showed that the toxicities of oximes might be related to their inactivation of mitochondrial oxidase enzymes and generation of reactive oxygen species.
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