Srinivasan Venkataraman, Doctrow Susan, Singh Vijay K, Whitnall Mark H
Radiation Countermeasures Program, Armed Forces Radiobiology Research Institute, Bethesda, Maryland Wisconsin Avenue, Bethesda, MD 20889-5603, USA.
Immunopharmacol Immunotoxicol. 2008;30(2):271-90. doi: 10.1080/08923970801925331.
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.
EUK - 189是一种双水杨醛缩乙二胺锰配合物，具有超氧化物歧化酶/过氧化氢酶模拟活性。在相对于全身钴 - 60γ射线照射（LD(90/30)剂量）的 - 24、 - 1、 +1或 +6小时，以皮下注射（sc；30或70 mg/kg）的方式给小鼠施用EUK - 189，并监测30天的存活率。在接受EUK - 189治疗的亚致死剂量照射小鼠中测量循环中的细胞计数和细胞因子。EUK - 189（70 mg/kg， - 24小时）提高了30天存活率，剂量降低系数（DRF）为1.15（p = 0.047，95%置信区间：1.053，1.244）。生理盐水处理组和EUK - 189处理组的LD(50/30)分别为7.96 Gy和9.13 Gy。与注射赋形剂的照射对照相比，药物治疗使受照射小鼠的总白细胞、嗜酸性粒细胞、淋巴细胞和血小板数量增加。EUK - 189未刺激所测试的任何细胞因子或趋化因子的产生。
