Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging

• Published in: Biochemical and biophysical research communications 2017-04, Vol.485 (4), p.802-806
• Main Authors: Emoto, Miho C., Matsuoka, Yuta, Yamada, Ken-ichi, Sato-Akaba, Hideo, Fujii, Hirotada G.
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Animals; Antioxidants - metabolism; Ascorbic Acid - metabolism; BIOMEDICAL RADIOGRAPHY; BRAIN; Brain - diagnostic imaging; Brain - metabolism; Cyclic N-Oxides - administration & dosage; Cyclic N-Oxides - chemistry; Cyclic N-Oxides - pharmacokinetics; ELECTRON SPIN RESONANCE; Electron Spin Resonance Spectroscopy - methods; EPR imaging; GLUTATHIONE; Glutathione - antagonists & inhibitors; Glutathione - metabolism; Magnetic Resonance Imaging - methods; Male; Maleates - administration & dosage; Maleates - pharmacology; MICE; Mice, Inbred C57BL; Molecular Structure; OXIDATION; Oxidation-Reduction - drug effects; Oxidative stress; PARAMAGNETISM; REACTION KINETICS; Redox status; ROS; Tissue Distribution
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2017.02.134

Glutathione (GSH) is the most abundant non-protein thiol that buffers reactive oxygen species in the brain. GSH does not reduce nitroxides directly, but in the presence of ascorbates, addition of GSH increases ascorbate-induced reduction of nitroxides. In this study, we used electron paramagnetic resonance (EPR) imaging and the nitroxide imaging probe, 3-methoxycarbonyl-2,2,5,5-tetramethyl-piperidine-1-oxyl (MCP), to non-invasively obtain spatially resolved redox data from mouse brains depleted of GSH with diethyl maleate compared to control. Based on the pharmacokinetics of the reduction reaction of MCP in the mouse heads, the pixel-based rate constant of its reduction reaction was calculated as an index of the redox status in vivo and mapped as a “redox map”. The obtained redox maps from control and GSH-depleted mouse brains showed a clear change in the brain redox status, which was due to the decreased levels of GSH in brains as measured by a biochemical assay. We observed a linear relationship between the reduction rate constant of MCP and the level of GSH for both control and GSH-depleted mouse brains. Using this relationship, the GSH level in the brain can be estimated from the redox map obtained with EPR imaging. •Redox status of glutathione-depleted mouse brain was examined with EPR imaging.•Redox status of mouse brain changed depending on glutathione (GSH) levels in brains.•Linear relationship between GSH levels and redox status in brains was found.•Using this relation, estimation of GSH levels in brains is possible from EPR images.