CCM-AMI, A POLYETHYLENE GLYCOL MICELLE WITH AMIFOSTINE, AS AN ACUTE RADIATION SYNDROME PROTECTANT IN C57BL/6 MICE
CCM-AMI, A POLYETHYLENE GLYCOL MICELLE WITH AMIFOSTINE, AS AN ACUTE RADIATION SYNDROME PROTECTANT IN C57BL/6 MICE
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DOI：
10.1097/hp.0000000000000326
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发表时间：
2015-09-01
期刊：
影响因子：
2.2
通讯作者：
Lin, Johnson
中科院分区：
文献类型：
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作者：
Chen, Chia-Hung;Kuo, Min-Liang;Lin, Johnson
急性辐射综合征是由辐射暴露引起的，例如在意外的核灾难中。必须开发安全有效的辐射防护剂、缓解剂和治疗药物，作为辐射暴露的医学对策。在这里，作者评价了CCM-Ami，一种用氨磷汀包封的新型聚乙二醇胶束，在Co-60源全身照射后的辐射防护性能。雄性C57 BL/6小鼠（6-8周龄）在暴露于7.2和8.5戈伊照射前90分钟静脉注射45 mg/kg（-1）CCM-Ami，剂量率为0.04戈伊/min（-1）。与赋形剂对照组和氨磷汀组相比，在预防性CCM-Ami给药后观察到生存益处和造血保护。药代动力学结果显示，在静脉注射后，WR-1065（氨磷汀的活性形式）在CCM-Ami处理的小鼠中的血浆浓度高于氨磷汀处理的小鼠。这些发现表明，CCM-Ami介导的造血保护在提高暴露于辐射毒性的小鼠的存活率方面起着关键作用，因此表明CCM-Ami是一种可以安全有效地用于核灾难的辐射防护剂。
Acute radiation syndrome results from radiation exposure, such as in accidental nuclear disasters. Safe and effective radioprotectants, mitigators, and treatment drugs must be developed as medical countermeasures against radiation exposure. Here, the authors evaluated CCM-Ami, a novel polyethylene glycol micelle encapsulated with amifostine, for its radioprotective properties after total-body irradiation from a Co-60 source. Male C57BL/6 mice (6-8 wk old) were intravenously injected with 45 mg kg(-1) of CCM-Ami 90 min before exposure to 7.2 and 8.5 Gy irradiation at a dose rate of 0.04 Gy min(-1). Both survival benefit and hematopoietic protection were observed after prophylactic CCM-Ami administration when compared with the effects measured in excipient control and amifostine groups. Pharmacokinetic results showed that after the intravenous injection, the plasma concentration of WR-1065, the active form of amifostine, was higher in CCM-Ami-treated mice than in amifostine-treated mice. These findings suggest that CCM-Ami-mediated hematopoietic protection plays a key role in enhancing survival of mice exposed to radiation toxicity and thus indicate that CCM-Ami is a radioprotectant that can be used safely and effectively in nuclear disasters.