A synthetic superoxide dismutase/catalase mimetic EUK-207 mitigates radiation dermatitis and promotes wound healing in irradiated rat skin. J Invest Dermatol 2013 Apr;133(4):1088-96
Date
11/30/2012Pubmed ID
23190879Pubmed Central ID
PMC3594042DOI
10.1038/jid.2012.410Scopus ID
2-s2.0-84875215759 (requires institutional sign-in at Scopus site) 45 CitationsAbstract
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.
Author List
Doctrow SR, Lopez A, Schock AM, Duncan NE, Jourdan MM, Olasz EB, Moulder JE, Fish BL, Mäder M, Lazar J, Lazarova ZAuthor
Edit Olasz MD, PhD Associate Professor in the Dermatology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsAntioxidants
Catalase
Disease Models, Animal
Gene Expression
Male
Molecular Mimicry
Organometallic Compounds
Oxidative Stress
Radiation Injuries, Experimental
Radiodermatitis
Rats
Rats, Inbred Strains
Skin
Superoxide Dismutase
Wound Healing
