title: Non-invasive imaging of the levels and effects of glutathione on the redox status of mouse brain using electron paramagnetic resonance imaging.
abstract: 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.
authors.affiliation: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido 060-8556, Japan; Department of Neurology, Sapporo Medical University School of Medicine, Sapporo, Hokkaido 060-8556, Japan.
authors.forename: Miho C
authors.initials: MC
authors.lastname: Emoto
authors.affiliation: Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan.
authors.forename: Yuta
authors.initials: Y
authors.lastname: Matsuoka
authors.affiliation: Physical Chemistry for Life Science Laboratory, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan; Japan Science and Technology Agency, PRESTO, Kawaguchi, Saitama 332-0012, Japan.
authors.forename: Ken-Ichi
authors.initials: KI
authors.lastname: Yamada
authors.affiliation: Department of Systems Innovation, Graduate School of Engineering Science, Oosaka University, Toyonaka, Oosaka 560-8531, Japan.
authors.forename: Hideo
authors.initials: H
authors.lastname: Sato-Akaba
authors.affiliation: Center for Medical Education, Sapporo Medical University, Sapporo, Hokkaido 060-8556, Japan. Electronic address: hgfujii@sapmed.ac.jp.
authors.forename: Hirotada G
authors.initials: HG
authors.lastname: Fujii
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D001921:Brain / Q000000981:diagnostic imaging / Q000378:metabolism*; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D004578:Electron Spin Resonance Spectroscopy / Q000379:methods*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D008297:Male; D008298:Maleates / Q000008:administration & dosage / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D015394:Molecular Structure; D010084:Oxidation-Reduction / Q000187:drug effects; D014018:Tissue Distribution
chemical_list: C585850:3-methoxycarbonyl-2,2,5,5-tetramethylpyrrolidine-1-oxyl; D000975:Antioxidants; D003497:Cyclic N-Oxides; D008298:Maleates; C014476:diethyl maleate; D005978:Glutathione; D001205:Ascorbic Acid
keywords: Brain; EPR imaging; Glutathione; Oxidative stress; ROS; Redox status