Davis Ryan M, Matsumoto Shingo, Bernardo Marcelino, Sowers Anastasia, Matsumoto Ken-Ichiro, Krishna Murali C, Mitchell James B
Radiation Biology Branch, Center for Cancer Research, National Institutes of Health, Bethesda, MD 20892, USA.
Free Radic Biol Med. 2011 Feb 1;50(3):459-68. doi: 10.1016/j.freeradbiomed.2010.11.028. Epub 2010 Dec 1.
Nitroxides are a class of stable free radicals that have several biomedical applications including radioprotection and noninvasive assessment of tissue redox status. For both of these applications, it is necessary to understand the in vivo biodistribution and reduction of nitroxides. In this study, magnetic resonance imaging was used to compare tissue accumulation (concentration) and reduction of two commonly studied nitroxides: the piperidine nitroxide Tempol and the pyrrolidine nitroxide 3-CP. It was found that 3-CP was reduced 3 to 11 times slower (depending on the tissue) than Tempol in vivo and that maximum tissue concentration varies substantially between tissues (0.6-7.2mM). For a given tissue, the maximum concentration usually did not vary between the two nitroxides. Furthermore, using electron paramagnetic resonance spectroscopy, we showed that the nitroxide reduction rate depends only weakly on cellular pO(2) in the oxygen range expected in vivo. These observations, taken with the marked variation in nitroxide reduction rates observed between tissues, suggest that tissue pO(2) is not a major determinant of the nitroxide reduction rate in vivo. For the purpose of redox imaging, 3-CP was shown to be an optimal choice based on the achievable concentrations and bioreduction observed in vivo.
氮氧化物是一类稳定的自由基，具有多种生物医学应用，包括辐射防护和组织氧化还原状态的无创评估。对于这两种应用，了解氮氧化物在体内的生物分布和还原情况是必要的。在本研究中，磁共振成像被用于比较两种常用研究的氮氧化物在组织中的积累（浓度）和还原情况：哌啶氮氧化物Tempol和吡咯烷氮氧化物3-CP。研究发现，在体内3-CP的还原速度比Tempol慢3至11倍（取决于组织），并且最大组织浓度在不同组织之间有很大差异（0.6 - 7.2mM）。对于给定的组织，两种氮氧化物的最大浓度通常没有差异。此外，使用电子顺磁共振光谱，我们表明在体内预期的氧范围内，氮氧化物的还原速率仅微弱地依赖于细胞pO₂。这些观察结果，结合在不同组织中观察到的氮氧化物还原速率的显著差异，表明组织pO₂不是体内氮氧化物还原速率的主要决定因素。就氧化还原成像而言，基于在体内观察到的可达到的浓度和生物还原情况，3-CP被证明是一个最佳选择。
