380 - In Vivo Brain Redox Status in Diethylmaleate-Treated Mice Using EPR Imaging

Abstract

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.