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Development of non-invasive evaluation of oxidative stress against living organisms by in vivo ESR

通过体内 ESR 对生物体氧化应激进行无创评估的进展

基本信息

批准号：
10357021
负责人：
OZAWA Toshihiko
金额：
$ 20.63万
依托单位：
National Institute of Radiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (A)
财政年份：
1998
资助国家：
日本
起止时间：
1998 至 2001
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10357021/
关键词：
L-band ESR oxidative stress trapping agent nitric oxide (NO)reactive oxygen species mouse nitroxyl radical ESR imaging X-バンドESR フリーラジカル重粒子線スピンクリアランス放射線

项目摘要

1)New trapping agents for nitric oxide(NO) were developed and their function was elucidated. Further, using these trapping agents NO was detected directly in living animals exposed by whole-body X-irradiation.2)It was shown that oxidative stress due to X-irradiation could be non-invasively evaluated in living animals by L-band ESR.3)As a novel nitroxyl probe, acetoxymethyl derivative of Carboxy-PROXYL which can be remained in the brain was developed. This new probe could be well distributed into the mouse brain than other probes. Further, imaging analyzer using ESR-CT method showed that this new probe could be gathered in the brain.4)A method of separable ESR-CT (electron spin resonance-computed tomography) imaging for multiple radical species was developed and applied to imaging of hydroxyl radical (OH) and nitric oxide (NO). As the result, the position and size of the individual images of OH and NO were in very good agreement with the findings for the sample.5)A simple and sensitive assay and a cellular bioimaging of a novel diaminofluorescein DAF-FM (3-amino-4-(N-methylamino)-2',7' -difluororescein) and its diacetate. It was found that this novel diaminofluorescein fluorometry should be useful not only for sensitive NO assay, but also for NO imaging in a variety of biological speciemens.6)In vivo electron spin resonance(ESR) imaging was applied to living mice after peroral administration of a nitroxide radical spin probe. A 3D ESR imaging procedure was applied in vivo in order to obtain the exact distribution of the spin probe in a living animal. The imaging pictures demonstrated that the administered spin probe was firstly located in the stomach, then delivered to the lliver, kidney and heart of the animal.

1)开发了新的一氧化氮（NO）捕获剂，并阐明了它们的功能。2）利用L-带ESR技术可以无创地检测活体动物体内X射线照射引起的氧化应激。3）开发了一种新的硝酰基探针--羧基-PROXYL的乙酰氧基甲基衍生物，该衍生物可以在脑内残留。这种新的探针可以比其他探针更好地分布到小鼠大脑中。利用ESR-CT方法的成像分析仪显示，该探针可在脑内聚集。4）建立了一种多自由基的可分离ESR-CT（electron spin resonance-computed tomography）成像方法，并将其应用于羟自由基（hydroxyl radical，OH）和一氧化氮（nitric oxide，NO）的成像。结果，OH和NO的单独图像的位置和大小与样品的发现非常一致。5）新的二氨基荧光素DAF-FM（3-氨基-4-（N-甲氨基）-2 '，7' -二荧光素）及其二乙酸酯的简单且灵敏的测定和细胞生物成像。结果表明，这种新型的二氨基荧光素荧光法不仅可用于灵敏的NO检测，而且可用于多种生物样品中的NO成像。6）将一种氮氧自由基自旋探针经口给药后，将活体电子自旋共振（ESR）成像应用于活体小鼠。为了获得自旋探针在活体动物中的准确分布，在体内应用了3D ESR成像程序。成像图像显示，所施用的自旋探针首先位于动物的胃中，然后递送到肝脏、肾脏和心脏。