| Co-Investigator(Kenkyū-buntansha) |
TAKESHITA Keizo Kyushu University, National Institute of Radiological Sciences, Chief Scientist, 放射線安全研究センター, 主任研究員 (70175438)
YASUI hisataka Kyushu University, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (20089923)
TAKESHITA Akira Kyushu University, Graduate School of Medical Sciences, Professor, 大学院・医学研究院, 教授 (30038814)
YAMADA Ken-ichi Kyushu University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究院, 助手 (60346806)
KOSHIISHI Ichiro Kyushu University, Graduate School of Pharmaceutical Sciences, Assistant Professor, 大学院・薬学研究院, 助教授 (20170235)
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| Research Abstract |
It is essential that the location of free radical generation corresponds to the specific target organ or tissue in order to investigate the relationship between the free radical generation and the initiation and/or progression of diseases. In this study, we developed the fused imaging system by the combination of Electron Spin Resonance Imaging(ESRI), which can visualize the free radical distribution, with Magnetic Resonance Imaging(MRI), which can provide anatomical information, for the purpose of analysis of oxidative stress-related diseases, and applied the system to in vivo measurement.
To build the co-registration system, a nitroxyl radical, which could be visualized by both images obtained using ESRI and MRI as a marker for positional calibration, was used, and the optimal methods in image construction were evaluated by simulation experiment because of the co-registration with high-precision. Nitroxyl radical solutions were administered to animals, and the fused images were obtain
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ed. These images demonstrate the differences in kinetics of nitroxyl radicals by the administration routes and the n-octanol/water partition coefficients(Po/w). Free radical generating reagents were orally administered just before the probe treatment, and the images, showing the free radical generation in stomach, were obtained.
We proposed an in vivo ESR/spin probe technique as a method for non-invasive and real-time analysis of in vivo free radical reaction and have evaluated the mechanism of free radical generation in the experimental models of diseases. In this study, gastrointestinal injury, diabetes and brain ischemia-reperfusion injury were selected as the models of oxidative stress-related diseases, and the location and kind of free radical generation were investigated. It was suggested that, using several kinds of nitroxyl radicals with different Po/w, hydroxyl radical was generated in an intracellular compartment in the model of indomethacin-induced gastric lesion injury and lipid radical was generated on the surfaces of cerebrovascular cell membranes in the model of brain ischemia-reperfusion injury.
From these findings, the fused imaging system by the combination of ESRI and MRI is thought to be the powerful tool to clear the in vivo free radical generation in the target organ and/or tissue. In the near future, it is expected that the application of this system enables us to elucidate the mechanism of free radical generation in oxidative stress-related diseases. Less
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