Soderberg L S, Barnett J B, Baker M L, Salari H, Sorenson R J
Department of Microbiology and Immunology, College of Pharmacy, University of Arkansas for Medical Sciences, Little Rock 72205.
Scand J Immunol. 1987 Nov;26(5):495-502. doi: 10.1111/j.1365-3083.1987.tb02283.x.
Copper(II)(3,5-diisopropylsalicylate)2 (Cu-DIPS), administered subcutaneously to mice at 80 mg/kg body weight, had marked radioprotective activity. Given 3 h before exposure to 8.0 Gy (800 rad) irradiation, Cu-DIPS increased the 42-day survival from 40% to 86%. Seven days after exposure to 8.0 Gy, there were severe reductions in spleen weight (73%) and cellularity (98%) in both Cu-DIPS- and vehicle-treated mice. Viable spleen cells collected 7 days after irradiation were totally unresponsive to mitogenic or antigenic stimulation regardless of Cu-DIPS or vehicle treatment, suggesting that Cu-DIPS did not prevent radiation-induced damage to mature lymphocytes. At 14 days, when Cu-DIPS-treated mice started to show improved survival over vehicle-treated mice, spleen weights and cellularity were 2.5- and 3.5-fold higher, respectively, in Cu-DIPS-treated mice. Treatment with Cu-DIPS not only enhanced splenic repopulation, but also accelerated the reappearance of both B and T cell reactivities. Spleen cell responsiveness to the B cell mitogen, lipopolysaccharide (LPS), and the T cell mitogen, concanavalin A (Con A), regenerated significantly faster in Cu-DIPS-treated mice. Cu-DIPS also significantly accelerated the regeneration of T-dependent antibody induction. Based on these assays of immunocompetence, Cu-DIPS-treated mice had, on average, a seven-fold greater capacity to respond to immune stimulation than vehicle-treated mice 24 days after irradiation.
以80毫克/千克体重皮下注射给小鼠的双(3,5-二异丙基水杨酸)铜(II)(Cu-DIPS)具有显著的辐射防护活性。在暴露于8.0戈瑞(800拉德)辐射前3小时给予Cu-DIPS,可使42天存活率从40%提高到86%。在暴露于8.0戈瑞辐射7天后,Cu-DIPS处理组和赋形剂处理组小鼠的脾脏重量(73%)和细胞数量(98%)均大幅降低。辐射7天后收集的存活脾细胞,无论Cu-DIPS或赋形剂处理,对有丝分裂原或抗原刺激均完全无反应,这表明Cu-DIPS不能预防辐射诱导的成熟淋巴细胞损伤。在第14天,当Cu-DIPS处理组小鼠开始显示出比赋形剂处理组小鼠更高的存活率时,Cu-DIPS处理组小鼠的脾脏重量和细胞数量分别高出2.5倍和3.5倍。Cu-DIPS处理不仅增强了脾脏再增殖,还加速了B细胞和T细胞反应性的重新出现。在Cu-DIPS处理组小鼠中,脾细胞对B细胞有丝分裂原脂多糖(LPS)和T细胞有丝分裂原刀豆球蛋白A(Con A)的反应性再生明显更快。Cu-DIPS还显著加速了T细胞依赖性抗体诱导的再生。基于这些免疫能力测定,在辐射后24天,Cu-DIPS处理组小鼠平均对免疫刺激的反应能力比赋形剂处理组小鼠高7倍。