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 (LD(90/30) 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). LD(50/30)s 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.
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland Wisconsin Avenue, Bethesda, MD 20889-5603, USA. Srinivasan@afrri.usuhs.mil
Venkataraman
V
Srinivasan
Susan
S
Doctrow
Vijay K
VK
Singh
Mark H
MH
Whitnall
D000818:Animals; D040761:Biomimetic Materials / Q000494:pharmacology*; D002374:Catalase; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005720:Gamma Rays / Q000009:adverse effects*; D007962:Leukocytes / Q000276:immunology; D008297:Male; D051379:Mice; D009942:Organometallic Compounds / Q000494:pharmacology*; D011837:Radiation-Protective Agents / Q000494:pharmacology*; D012459:Salicylates / Q000494:pharmacology*; D013482:Superoxide Dismutase
C436526:EUK-189; D009942:Organometallic Compounds; D011837:Radiation-Protective Agents; D012459:Salicylates; D002374:Catalase; D013482:Superoxide Dismutase