Spinnokinetic Analyses of Blood Disposition and Biliary Excretion of Nitric Oxide (NO)-Fe(II)-N-(Dithiocarboxy)sarcosine Complex in Rats: BCM-ESR and BEM-ESR Studies
Spinnokinetic Analyses of Blood Disposition and Biliary Excretion of Nitric Oxide (NO)-Fe(II)-N-(Dithiocarboxy)sarcosine Complex in Rats: BCM-ESR and BEM-ESR Studies
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DOI：
10.1080/10715760412331273449
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发表时间：
2004-10
影响因子：
3.3
通讯作者：
H. Yasui;S. Fujii;T. Yoshimura;H. Sakurai
中科院分区：
文献类型：
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作者：
H. Yasui;S. Fujii;T. Yoshimura;H. Sakurai
众所周知，一氧化氮（NO）在动物中具有多种生物和生理功能。基于铁(II)-二硫代氨基甲酸酯与NO发生反应的事实，提出了一种铁(II)- n -（二硫代羧基）肌氨酸配合物（Fe(II)- dtcs）作为内源性NO的捕集剂。然而，NO-Fe(II)-二硫代氨基甲酸酯配合物在实验动物体内的定量药动学研究相当有限。本文描述了静脉注射NO-Fe(II)-N-DTCS复合物后大鼠血液和胆汁中定量药代动力学特征的结果。为此，我们采用了两种体内方法，即(1)体内血液循环监测-电子自旋共振（BCM-ESR）和(2)体内胆汁排泄监测-电子自旋共振（BEM-ESR）。我们监测了由于亚硝基铁在循环血液和胆汁流动中的实时ESR信号。NO-Fe(II)-DTCS引起的ESR信号在新鲜血液和胆汁等生物系统中是稳定的。在体内BCM-和BEM-ESR中，根据两室和肝胆运输模型计算药代动力学参数。研究还表明，该化合物广泛分布于外周器官，部分排泄到胆汁中。我们将一种追踪自旋浓度的动力学方法命名为自旋动力学，该方法将有助于检测和定量Fe(II)-DTCS给药动物体内内源性NO的产生。
Nitric oxide (NO) is well known to have a wide variety of biological and physiological functions in animals. On the basis of the fact that Fe(II)-dithiocarbamates react with NO, a Fe(II)-N-(dithiocarboxy)sarcosine complex (Fe(II)-DTCS) was proposed as a trapping agent for endogenous NO. However, quantitative pharmacokinetic investigation for NO-Fe(II)-dithiocarbamate complexes in experimental animals has been quite limited. This paper describes the results on the quantitative pharmacokinetic features of a NO-Fe(II)-N-DTCS in both the blood and bile of rats following intravenous (i.v.) administration of the complex. For this purpose, we applied two in vivo methods, i.e. (1) in vivo blood circulation monitoring-electron spin resonance (BCM-ESR) which previously developed, and (2) in vivo biliary excretion monitoring-electron spin resonance (BEM-ESR). We monitored real-time ESR signals due to nitrosyl-iron species in the circulating blood and bile flow. The ESR signal due to NO-Fe(II)-DTCS was stable in biological systems such as the fresh blood and bile. In in vivo BCM- and BEM-ESR, the pharmacokinetic parameters were calculated on the basis of the two-compartment and hepatobiliary transport models. The studies also revealed that the compound is widely distributed in the peripheral organs and partially excreted into the bile. We named a kinetic method to follow spin concentrations as spinnokinetics and this method will be useful for detecting and quantifying the endogenously generated NO in Fe(II)-DTCS administered animals.