Novel Pharmacokinetic Measurement Using Electron Paramagnetic Resonance Spectroscopy and Simulation of in Vivo Decay of Various Nitroxyl Spin Probes in Mouse Blood
Novel Pharmacokinetic Measurement Using Electron Paramagnetic Resonance Spectroscopy and Simulation of in Vivo Decay of Various Nitroxyl Spin Probes in Mouse Blood
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使用电子顺磁共振波谱进行新型药代动力学测量并模拟小鼠血液中各种硝酰基自旋探针的体内衰变
DOI：
10.1124/jpet.104.066647
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发表时间：
2004
影响因子：
3.5
通讯作者：
James B. Mitchell
中科院分区：
文献类型：
--
作者：
Ken;M. Krishna;James B. Mitchell
本文介绍了一种用X波段（9.4GHz）电子顺磁共振谱仪测量小鼠循环血液中顺磁自旋探针浓度随时间变化的新方法。使用这种技术，几个硝酰基自旋探针的药代动力学进行了研究。衰减曲线也独立地模拟使用药代动力学特性以及氧化还原介导的因素，负责将硝酰基自由基转化为相应的羟胺。最后，硝酰基自由基作为体内氧化还原状态的探针和辐射防护的适用性进行了描述。研究表明，六元哌啶硝酰基适合于估计循环中的氧化还原状态，而五元吡咯烷硝酰基自由基适合于组织氧化还原状态测定。为了选择性保护正常组织而不是癌症/肿瘤免受辐射，优选在正常组织中羟胺的有效再氧化。模拟结果表明，对于氨基甲酰基-PROXYL，仅给予自由基形式可能提供辐射保护，而不是羟胺。然而，TEMPOL的羟胺形式，即，TEMPOL-H，由于体内有效的再氧化，可以提供与自由基形式相似的辐射保护。
A novel approach to measure the time course of paramagnetic spin probe concentration in the circulating blood of a living mouse using X-band (9.4 GHz) electron paramagnetic resonance spectrometer is described. Using this technique, the pharmacokinetics of several nitroxyl spin probes was examined. The decay profiles were also independently simulated using pharmacokinetic properties as well as redox-mediated factors responsible in converting the nitroxyl radicals to the corresponding hydroxylamines. Finally, suitability of nitroxyl radicals as the probes of in vivo redox status and for radioprotection was described. The studies indicate that the six-member piperidine nitroxyls are suitable for estimating redox status in the circulation, whereas the five-member pyrrolidine nitroxyl radicals are suited for tissue redox status determination. For selective protection against radiation of normal tissues rather than cancer/tumor, efficient reoxidation of the hydroxylamine in normal tissue is preferable. Simulation results showed that for carbamoyl-PROXYL, only administration of the radical form might give radioprotection and not the hydroxylamine. However, the hydroxylamine form of TEMPOL, i.e., TEMPOL-H, may give similar radioprotection as the radical form due to efficient reoxidation in vivo.
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DOI：
--
发表时间：
2001
期刊：
--
影响因子：
--
作者：
P. Kuppusamy;G. Ilangovan;A. Cardounel;J. Zweier;Ken‐ichi Yamada;M. Krishna;James B. Mitchell
通讯作者：
P. Kuppusamy;G. Ilangovan;A. Cardounel;J. Zweier;Ken‐ichi Yamada;M. Krishna;James B. Mitchell
DOI：
10.1006/bbrc.1994.1806
发表时间：
1994-06-15
影响因子：
3.1
作者：
KOMAROV, AM;JOSEPH, J;LAI, CS
通讯作者：
LAI, CS
TEMPOL 可防止接受 X 光检查的兔子晶状体 DNA 链断裂和白内障。
DOI：
--
发表时间：
1998
期刊：
Investigative ophthalmology & visual science.
影响因子：
--
作者：
Sasaki,H;Lin,LR;Yokoyama,T;Sevilla,MD;Reddy,VN;Giblin,FJ
通讯作者：
Giblin,FJ
使用电子顺磁共振成像非侵入性体内氧化还原状态的可行性和评估。
DOI：
10.1080/j.1600-0455.2002.430418.x
发表时间：
2002
期刊：
Acta radiologica (Stockholm, Sweden : 1987)
影响因子：
--
作者：
Yamada,K-I;Kuppusamy,P;English,S;Yoo,J;Irie,A;Subramanian,S;Mitchell,JB;Krishna,MC
通讯作者：
Krishna,MC