In Vivo Brain Redox Status in Diethylmaleate-Treated Mice Using EPR Imaging.
In Vivo Brain Redox Status in Diethylmaleate-Treated Mice Using EPR Imaging.
复制标题
使用 EPR 成像观察马来酸二乙酯处理的小鼠体内脑氧化还原状态。
DOI：
10.1016/j.freeradbiomed.2016.10.421
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发表时间：
2016
影响因子：
7.4
通讯作者：
Ken-ichi Yamada
中科院分区：
文献类型：
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作者：
Hirotada G Fujii;Miho C Emoto;Yuta Matsuoka;Ken-ichi Yamada
在正常生理条件下，氧化损伤是通过抗氧化网络调节ROS来防止的。脑中的主要抗氧化剂是抗坏血酸（阿萨）和谷胱甘肽（GSH），并且这些抗氧化剂的水平根据疾病状态而变化。氮氧自由基是氧化还原敏感性化合物，在体内存在阿萨和GSH时会被还原。因此，EPR成像与氮氧自由基已被用来可视化氧化性脑疾病的氧化还原状态，但还原型谷胱甘肽的氮氧自由基的还原反应的作用还不清楚。在本研究中，使用GSH耗竭与马来酸二乙酯（DEM）的小鼠模型，GSH在脑氧化还原状态的作用进行了检查，非侵入性的EPR成像与血脑屏障渗透3-甲氧羰基-PROXYL（MCP）。计算对照和DEM处理的小鼠头部中MCP的基于像素的减少速率，并绘制为氧化还原图。得到的氧化还原图谱清楚地表明，MCP的还原率显着下降，在DEM处理的小鼠脑。GSH测定显示，与未处理的小鼠相比，DEM处理的小鼠脑中GSH水平显著降低。GSH水平的变化与小鼠脑图像氧化还原状态的变化密切相关。
Under normal physiological conditions, oxidative damage is prevented by the regulation of ROS by the antioxidant network. Major antioxidants in brain are ascorbic acid (AsA) and glutathione (GSH), and the levels of these antioxidants change depending on the disease state. Nitroxides are redox-sensitive compounds and reduced in vivo in the presence of AsA and GSH. Therefore, EPR imaging with nitroxides has been used to visualize the redox status in oxidative brain diseases, but the role of GSH on the reduction reaction of nitroxides is not clear. In the present study, using the mouse model of GSH depletion with diethylmaleate (DEM), the role of GSH in the brain redox status was examined non-invasively by EPR imaging with blood brain barrier-permeable 3-methoxycarbonyl-PROXYL (MCP). The pixel-based reduction rates of MCP in control and DEM-treated mouse heads were calculated and plotted as a redox map. The obtained redox map clearly showed that reduction rates of MCP significantly decreased in DEM-treated mouse brain. The GSH assay showed a significant reduction of GSH levels in DEM-treated mouse brain compared with untreated one. Alteration of the GSH level correlates well with the change in redox status of mouse brain image.