In vivo radioprotection and effects on blood pressure of the stable free radical nitroxides
In vivo radioprotection and effects on blood pressure of the stable free radical nitroxides
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DOI：
10.1016/s0360-3016(98)00317-4
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发表时间：
1998-11-01
影响因子：
7
通讯作者：
Mitchell, JB
中科院分区：
文献类型：
--
作者：
Hahn, SM;DeLuca, AM;Mitchell, JB
目的：筛选几种具有体内辐射防护作用的水溶性氮氧化物，评价其药理作用，并测定其对全身血压的影响，为探讨体内辐射防护机制提供手段。方法与材料：筛选了多种水溶性氮氧化物在单一辐射剂量下对C3H小鼠的体内辐射防护作用。在全身照射剂量9Gy10分钟前，经腹膜途径给予选定的氮氧化物，用电子顺磁共振波谱(EPR)测定全血中氮氧化物的浓度。结果：与生理盐水对照组相比，所研究的所有氮氧化物均表现出辐射防护作用。在10-20分钟内，包括坦普尔在内的6元哌环氮氧化物被迅速还原为失活的羟胺。随着时间的推移，5元环氮氧化合物的还原速度变得更慢。与所研究的其他氮氧化物相比，5元环3-氨甲酰-丙氧基在腹膜腔给药后并没有显著降低全身血压。结论：除了3-氨基甲酰-丙氧基外，所有化合物在体内的辐射防护作用至少部分是通过诱导低血压和骨髓缺氧来解释的，3-氨基甲酰-丙氧基在体内提供的辐射防护与坦普尔相似，与其他氮氧化物相比对血压的影响很小，可能还有其他辐射防护机制，包括清除自由基。应进一步评估3-氨基甲酰-丙氧基作为全身辐射防护剂的作用，(C)1998年埃尔塞维尔科学公司。
Purpose: The purpose of this study was to screen several water soluble nitroxides for in vivo radioprotection, to evaluate their pharmacology, and to measure the effect of nitroxides on systemic blood pressure as a means of exploring the mechanism of in vivo radioprotection,Methods and Materials: A number of water soluble nitroxides were screened for in vivo radioprotection in C3H mice at a single radiation dose. Selected nitroxides were administered by the intraperitoneal route 10 minutes prior to a whole body radiation dose of 9 Gy, Electron paramagnetic resonance spectroscopy (EPR) was used to measure whole blood levels of nitroxides. The nitroxides were evaluated for effects on systemic blood pressure in C3H mice.Results: All of the nitroxides studied demonstrated radioprotection compared to saline-treated controls. The 6-membered piperidine ring nitroxides including Tempol were reduced to the inactive hydroxylamine rapidly over 10-20 minutes. The 5-membered ring nitroxides were reduced more slowly over time. The 5-membered ring 3-carbamoyl-PROXYL did not produce a substantial decrease in systemic blood pressure after intraperitoneal administration compared to the other nitroxides studied. 3-carbamoyl-PROXYL was further evaluated over a range of whole body radiation doses and was found to provide radioprotection,Conclusion: All of the nitroxides studied provided radioprotection, In vivo radioprotection for all of the compounds except 3-carbamoyl-PROXYL may be at least partially explained by the induction of hypotension and bone marrow hypoxia, 3-carbamoyl-PROXYL provided in vivo radioprotection similar in magnitude to Tempol and had little effect on blood pressure compared to the other nitroxides, Other mechanisms for radioprotection, including scavenging of free radicals are likely. 3-carbamoyl-PROXYL should be evaluated further as a systemic radioprotector, (C) 1998 Elsevier Science Inc.