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 h 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 plays a critical role in the progression of radiation-induced skin injury, and that the injury can be mitigated by appropriate antioxidant compounds administered 48 h after exposure.

Therapeutic and prophylactic effects of strontium on radiotherapy-induced skin toxicity in rats

“…Ketamine HCl was administered for anesthesia before radiation, measurements of the rats were taken by simulation on the prepared foam assembly, and the arms and legs were fixed with adhesive tape. RT region was established as the skin of the thorax (back) consisting of 10% of the total body of the rats [6][7][8][9] . Maximum two rats were irradiated at one time.…”

A review of radiation countermeasures focusing on injury-specific medicinals and regulatory approval status: part I. Radiation sub-syndromes, animal models and FDA-approved countermeasures

“…Rats have been used to study radiationinduced pneumonitis and lung fibrosis (Ghosh et al 2009;Gao et al 2012). A study using a single high dose of TBI capable of inducing pneumonitis, a dose relevant to radiological terrorism or nuclear accidents, was used to demonstrate that a short course of EUK-207, a synthetic superoxide dismutase (SOD)/catalase mimetic, starting 7 d post-irradiation and stopping before appearance of pneumonitis, mitigates radiationinduced pneumonitis and pulmonary fibrosis, as well as increased survival in rats Doctrow et al 2013). EUK-207 mitigation of lung fibrosis was also demonstrated using a model of whole-thoracic irradiation.…”

The Use of Antioxidants in Radiotherapy-Induced Skin Toxicity

“…Modifications made to the structure of the enzyme, as well as its delivery vehicle have improved its applicability as a therapy by increasing the duration of action and increasing the availability of the enzyme. [48][49][50] The clinical success achieved with this potent antioxidant has stimulated interest in exploring natural occurring and more affordable antioxidant substances.…”