title: Mitigating effect of EUK-207 on radiation-induced cognitive impairments.
abstract: The brain could be exposed to irradiation as part of a nuclear accident, radiological terrorism (dirty bomb scenario) or a medical radiological procedure. In the context of accidents or terrorism, there is considerable interest in compounds that can mitigate radiation-induced injury when treatment is initiated a day or more after the radiation exposure. As it will be challenging to determine the radiation exposure an individual has received within a relatively short time frame, it is also critical that the mitigating agent does not negatively affect individuals, including emergency workers, who might be treated, but who were not exposed. Alterations in hippocampus-dependent cognition often characterize radiation-induced cognitive injury. The catalytic ROS scavenger EUK-207 is a member of the class of metal-containing salen manganese (Mn) complexes that suppress oxidative stress, including in the mitochondria, and have been shown to mitigate radiation dermatitis, promote wound healing in irradiated skin, and mitigate vascular injuries in irradiated lungs. As the effects of EUK-207 against radiation injury in the brain are not known, we assessed the effects of EUK-207 on sham-irradiated animals and the ability of EUK-207 to mitigate radiation-induced cognitive injury. The day following irradiation or sham-irradiation, the mice started to receive EUK-207 and were cognitively tested 3 months following exposure. Mice irradiated at a dose of 15Gy showed cognitive impairments in the water maze probe trial. EUK-207 mitigated these impairments while not affecting cognitive performance of sham-irradiated mice in the water maze probe trial. Thus, EUK-207 has attractive properties and should be considered an ideal candidate to mitigate radiation-induced cognitive injury.
authors: Department of Behavioral Neuroscience, L470, Oregon Health and Science University, Portland, OR 97239, USA; Departments of Neurology and Radiation Medicine, Division of Neuroscience, ONPRC, L470, Oregon Health and Science University, Portland, Oregon 97239, USA. Electronic address: raberj@ohsu.edu.
authors: J
authors: J
authors: Raber
authors: Department of Behavioral Neuroscience, L470, Oregon Health and Science University, Portland, OR 97239, USA.
authors: M J
authors: MJ
authors: Davis
authors: Department of Behavioral Neuroscience, L470, Oregon Health and Science University, Portland, OR 97239, USA.
authors: T
authors: T
authors: Pfankuch
authors: Pulmonary Center, Boston University School of Medicine, MA 02215, USA.
authors: R
authors: R
authors: Rosenthal
authors: Pulmonary Center, Boston University School of Medicine, MA 02215, USA.
authors: S R
authors: SR
authors: Doctrow
authors: Department of Radiation Oncology, Medical College of Wisconsin, Milwaukee, WI, USA.
authors: J E
authors: JE
authors: Moulder
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003072:Cognition Disorders / Q000188:drug therapy* / Q000209:etiology*; D003213:Conditioning, Psychological / Q000187:drug effects; D004307:Dose-Response Relationship, Radiation; D005239:Fear / Q000187:drug effects; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000627:therapeutic use*; D011833:Radiation Injuries, Experimental / Q000150:complications*; D013482:Superoxide Dismutase / Q000378:metabolism; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: C476761:EUK 207; D009942:Organometallic Compounds; C002744:3-nitrotyrosine; D014443:Tyrosine; D013482:Superoxide Dismutase