Marković Snezana D, Vukajlović Miroslava Dj, Ognjanović Branka I, Stajn Andras S, Zikić Radoslav V, Saicić Zorica S, Radojicić Ratko M, Jones David R, Spasić Mihajlo B
Institute of Biology and Ecology, Faculty of Science, University of Kragujevac, 34000 Kragujevac, Serbia and Montenegro.
Cell Biochem Funct. 2007 May-Jun;25(3):251-8. doi: 10.1002/cbf.1320.
After enzymic biotransformation, molsidomine (MO) acts via the metabolite 3-morpholinosydnonimine (SIN-1) through spontaneous liberation of nitric oxide (NO) and superoxide (O(2)(.-)). The aim of this study was to compare the effects of MO and its active metabolite SIN-1 on the redox status of rat erythrocytes and reticulocytes. Rat erythrocyte as well as reticulocyte-rich red blood cell (RBC) suspensions were aerobically incubated (2 h, 37 degrees C) without (control) or in the presence of different concentrations of MO or SIN-1. In rat erythrocytes, biotransformation of MO resulted in the production of NO and nitroxyl (NO(-)). Endogenous superoxide anion (O(2)(.-)) participated in peroxynitrite generation. SIN-1 simultaneously liberated NO and O(2)(.-), which formed peroxynitrite (at least in part), but the liberated NO predominantly reacted with haemoglobin, forming methaemoglobin in erythrocytes. In reticulocytes, MO and SIN-1 caused an increase in the levels of both nitrite and 3-nitrotyrosine (an indicator of peroxynitrite), whereas they decreased the level of O(2)(.-). In reticulocytes, MO was metabolized into SIN-1 which led to the generation of NO, which reacted with O(2)(.-) (endogenous or exogenous) forming reactive nitrogen species. In conclusion, there are two metabolic pathways for MO biotransformation: one causing NO and NO(-) generation predominantly in erythrocytes and the other, via SIN-1 metabolism, in reticulocytes. The main difference between the action of MO and SIN-1 was that the latter caused oxidative damage in RBCs.
在酶促生物转化后，吗多明（MO）通过代谢产物3 - 吗啉代西多胺（SIN - 1）起作用，一氧化氮（NO）和超氧阴离子（O₂⁻）会自发释放。本研究的目的是比较MO及其活性代谢产物SIN - 1对大鼠红细胞和网织红细胞氧化还原状态的影响。将大鼠红细胞以及富含网织红细胞的红细胞（RBC）悬液在有氧条件下（2小时，37℃）孵育，分别在无（对照）或存在不同浓度的MO或SIN - 1的情况下进行。在大鼠红细胞中，MO的生物转化导致NO和硝酰阴离子（NO⁻）的产生。内源性超氧阴离子（O₂⁻）参与了过氧亚硝酸根的生成。SIN - 1同时释放NO和O₂⁻，它们至少部分形成了过氧亚硝酸根，但释放的NO主要与血红蛋白反应，在红细胞中形成高铁血红蛋白。在网织红细胞中，MO和SIN - 1导致亚硝酸盐和3 - 硝基酪氨酸（过氧亚硝酸根的指标）水平升高，而它们降低了O₂⁻的水平。在网织红细胞中，MO代谢为SIN - 1，导致NO的产生，NO与O₂⁻（内源性或外源性）反应形成活性氮物种。总之，MO生物转化有两条代谢途径：一条主要在红细胞中导致NO和NO⁻的产生，另一条通过SIN - 1代谢，在网织红细胞中起作用。MO和SIN - 1作用的主要区别在于后者会对红细胞造成氧化损伤。
