Evaluation of EUK-189, a synthetic superoxide dismutase/catalase mimetic as a radiation countermeasure

EUK-189, a salen-manganese complex and superoxide dismutase/catalase mimetic, was administered subcutaneously (sc; 30 or 70 mg/kg) to mice at -24, -1, +1, or +6 h relative to whole-body cobalt-60 gamma irradiation (LD90/30 dose), and survival was monitored for 30 days. Cell counts and cytokines in circulation were measured in sublethally irradiated mice treated with EUK-189. EUK-189 (70 mg/kg, -24 h) enhanced 30-day survival with a dose reduction factor (DRF) of 1.15 (p = 0.047, 95% confidence limits: 1.053, 1.244). LD50/30s were 7.96 and 9.13 Gy for saline- and EUK-189-treated groups, respectively. Drug treatment was associated with elevations in numbers of total white blood cells, eosinophils, lymphocytes, and platelets in irradiated mice, compared to vehicle-injected, irradiated controls. EUK-189 did not stimulate production of any cytokine or chemokine tested.