| Project/Area Number |
24590393
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pathological medical chemistry
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| Research Institution | Nippon Medical School |
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Principal Investigator |
OKAMOTO Ken 日本医科大学, 医学部, 准教授 (60267143)
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| Co-Investigator(Kenkyū-buntansha) |
KUSANO Teruo 日本医科大学, 医学部, 助教 (30434129)
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| Project Period (FY) |
2012-04-01 – 2015-03-31
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| Project Status |
Completed (Fiscal Year 2014)
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| Budget Amount *help |
¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000)
Fiscal Year 2014: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
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| Keywords | キサンチン酸化還元酵素 / 活性酸素 / 虚血再灌流障害 / 抗痛風薬 / 全脳虚血 / キサンチン酸化酵素 / キサンチン脱水素酵素 / 脳虚血 / 一酸化窒素 / xanthine oxidase / xanthine dehydrogenase / repurfusion injury / brain ischemia / febuxostat |
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| Outline of Final Research Achievements |
Xanthine oxidoreductase (XOR) inhibitors are reported to protect tissues from damage caused by reactive oxygen species (ROS) by inhibiting its production through XOR inhibition. We analyzed the effects of inhibitors in decreasing global severe cerebral I/R damage in mice. Mice were divided into three groups: a placebo group, an allopurinol group, and a febuxostat group. Each groups was performed pathological examination on the CA1 and CA2 regions of the hippocampus 4 days after I/R surgery, which revealed that the number of neuronal cells decreased in the 14-min occlusion model in both regions but the drugs administered to prevent this damage were not effective. One of the reasons for the less effectiveness of XOR inhibitors to control severe whole brain ischemia in mouse model is due to the low levels of expression of XOR in the mouse brain.
We analyzed molecular mechanism of ROS production by XOR using C-terminal deleted mutant, and published the result as an original article.
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