title: A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin.
abstract: In the event of a radionuclear attack or nuclear accident, the skin would be the first barrier exposed to radiation, though skin injury can progress over days to years following exposure. Chronic oxidative stress has been implicated as being a potential contributor to the progression of delayed radiation-induced injury to skin and other organs. To examine the causative role of oxidative stress in delayed radiation-induced skin injury, including impaired wound healing, we tested a synthetic superoxide dismutase (SOD)/catalase mimetic, EUK-207, in a rat model of combined skin irradiation and wound injury. Administered systemically, beginning 48 hours after irradiation, EUK-207 mitigated radiation dermatitis, suppressed indicators of tissue oxidative stress, and enhanced wound healing. Evaluation of gene expression in irradiated skin at 30 days after exposure revealed a significant upregulation of several key genes involved in detoxication of reactive oxygen and nitrogen species. This gene expression pattern was primarily reversed by EUK-207 therapy. These results demonstrate that oxidative stress has a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 hours after exposure.
authors.affiliation: Department of Medicine, Boston University School of Medicine, Boston, MA, USA.
authors.forename: Susan R
authors.initials: SR
authors.lastname: Doctrow
authors.forename: Argelia
authors.initials: A
authors.lastname: Lopez
authors.forename: Ashley M
authors.initials: AM
authors.lastname: Schock
authors.forename: Nathan E
authors.initials: NE
authors.lastname: Duncan
authors.forename: Megan M
authors.initials: MM
authors.lastname: Jourdan
authors.forename: Edit B
authors.initials: EB
authors.lastname: Olasz
authors.forename: John E
authors.initials: JE
authors.lastname: Moulder
authors.forename: Brian L
authors.initials: BL
authors.lastname: Fish
authors.forename: Marylou
authors.initials: M
authors.lastname: Mäder
authors.forename: Jozef
authors.initials: J
authors.lastname: Lazar
authors.forename: Zelmira
authors.initials: Z
authors.lastname: Lazarova
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D002374:Catalase / Q000378:metabolism; D004195:Disease Models, Animal; D015870:Gene Expression / Q000187:drug effects / Q000502:physiology; D008297:Male; D018716:Molecular Mimicry / Q000502:physiology; D009942:Organometallic Compounds / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects* / Q000235:genetics; D011833:Radiation Injuries, Experimental / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011855:Radiodermatitis / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains; D012867:Skin / Q000098:blood supply / Q000473:pathology / Q000528:radiation effects; D013482:Superoxide Dismutase / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
chemical_list: D000975:Antioxidants; C476761:EUK 207; D009942:Organometallic Compounds; D002374:Catalase; D013482:Superoxide Dismutase