Competition of nitroxyl contrast agents as an in vivo tissue redox probe: comparison of pharmacokinetics by the bile flow monitoring (BFM) and blood circulating monitoring (BCM) methods using X-band EPR and simulation of decay profiles.
Competition of nitroxyl contrast agents as an in vivo tissue redox probe: comparison of pharmacokinetics by the bile flow monitoring (BFM) and blood circulating monitoring (BCM) methods using X-band EPR and simulation of decay profiles.
复制标题
硝酰基造影剂作为体内组织氧化还原探针的竞争：使用 X 波段 EPR 和模拟衰减曲线，通过胆汁流量监测 (BFM) 和血液循环监测 (BCM) 方法比较药代动力学。
DOI：
10.1002/mrm.20958
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发表时间：
2006
期刊：
影响因子：
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通讯作者：
Endo,Kazutoyo
中科院分区：
文献类型：
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作者：
Okajo,Aya;Matsumoto,Ken-ichiro;Mitchell,JamesB;Krishna,MuraliC;Endo,Kazutoyo
在电子顺磁共振（EPR）和/或核磁共振成像中用作组织氧化还原敏感造影剂的硝酰基自由基应满足以下两个条件：1）分子快速分散到组织中，2）通过自由基的简单还原而发生顺磁损失。将几种硝酰基造影剂的药代动力学趋势与使用 X 波段 EPR 的胆汁流量监测 (BFM) 和血液循环监测 (BCM) 方法获得的结果进行了比较。硝酰自由基（TEMPO、TEMPONE（oxo-TEMPO）和氨基-TEMPO）在胆汁中显示出额外的 EPR 信号，这些信号归因于通过肝脏从血液输送到胆汁期间形成的代谢物。然而，高度亲水性的 CAT-1（三甲基铵-TEMPO）具有较低的膜渗透性，在胆汁中的浓度极低。具有羧基部分的探针，例如羧基-TEMPO和羧基-PROXYL，可以通过阴离子转运蛋白转运到肝细胞中。根据实验数据模拟了硝酰基自由基的 EPR 信号衰减曲线。我们之前应用于小鼠血液的模拟经过修改，可以同时拟合大鼠获得的 BFM 和 BCM 实验结果。模拟数据显示药代动力学机制的简单/复杂性，并且氨基甲酰基-PROXYL 和 TEMPOL（羟基-TEMPO）是评估组织氧化还原状态的合适造影剂。 Magn Reson Med，2006 年。2006 年出版 Wiley‐Liss, Inc.
Nitroxyl radicals used as tissue redox‐sensitive contrast agents in electron paramagnetic resonance (EPR) and/or NMR imaging should satisfy the following two conditions: 1) the molecules disperse into tissues rapidly, and 2) paramagnetic loss occurs by simple reduction of the radical. The pharmacokinetic trends of several nitroxyl contrast agents were compared with the results obtained by bile flow monitoring (BFM) and blood circulation monitoring (BCM) methods using X‐band EPR. The nitroxyl radicals (TEMPO, TEMPONE (oxo‐TEMPO), and amino‐TEMPO) showed additional EPR signals in the bile that were attributed to metabolites formed during transport from blood to bile through the liver. However, the highly hydrophilic CAT‐1 (trimethylammonium‐TEMPO), which has low membrane permeability, showed minimal concentration in the bile. Probes that have carboxyl moiety, such as carboxy‐TEMPO and carboxy‐PROXYL, can be transported via anion transporter into hepatic cells. The EPR signal decay profiles of the nitroxyl radicals were simulated based on the experimental data. The simulation, which we previously applied to mouse blood, was modified to simultaneously fit the experimental results of BFM and BCM obtained with rats. The simulation data showed the simplicity/complexity of the pharmacokinetic mechanisms and that carbamoyl‐PROXYL and TEMPOL (hydroxy‐TEMPO) are suitable contrast agents for assessing tissue redox status. Magn Reson Med, 2006. Published 2006 Wiley‐Liss, Inc.