Partial volume rat lung irradiation: The protective/mitigating effects of Eukarion-189, a superoxide dismutase–catalase mimetic

Abstract

Background and purpose The purpose of the current study was to elucidate the protective/mitigating effects of a SOD–catalase mimetic, Eukarion-189 (EUK-189), on DNA damage in rat lung following irradiation. The particular focus of these studies was the efficacy of EUK-189 when given after irradiation (mitigation). Patients and methods We exposed whole or lower lungs of female Sprague–Dawley rats to doses ranging from 10 to 20.5 Gray (Gy) of 60Co gamma rays. Animals in the EUK-189 treated groups received 2 or 30 mg/kg intraperitoneally (i.p.) at various times postirradiation (PI). A micronucleus assay was used to examine DNA damage at various times up to 16 weeks PI. Results Our results indicated that EUK-189 administration after irradiation is effective at reducing micronucleus formation in lung fibroblasts at various times following radiation exposure. Treatment with EUK-189 in the first 3 days after thoracic irradiation did not, however, modify the dose required to cause severe morbidity at 2–3 months after irradiation. Conclusions The protection produced when Eukarion-189 was given shortly after irradiation suggests that DNA damage observed in the lung may be caused by chronic production of ROS induced by a chronic inflammatory response initiated by the radiation treatment. We speculate that our failure to observe protection against severe morbidity at 2–3 months may be because our treatment regime only blocked the initial wave of ROS production and that treatment needs to be more prolonged to suppress the effects of a chronic inflammatory response.