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A comparative study of the effects of molsidomine and 3‐morpholinosydnonimine on the redox status of rat erythrocytes and reticulocytes
Author(s) -
Marković Snežana D.,
Vukajlović Miroslava Dj.,
Ognjanović Branka I.,
Štajn Andraš Š.,
Žikić Radoslav V.,
Saičić Zorica S.,
Radojičić Ratko M.,
Jones David R.,
Spasić Mihajlo B.
Publication year - 2006
Publication title -
cell biochemistry and function
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.933
H-Index - 61
eISSN - 1099-0844
pISSN - 0263-6484
DOI - 10.1002/cbf.1320
Subject(s) - peroxynitrite , molsidomine , chemistry , nitric oxide , superoxide , metabolite , biotransformation , biochemistry , nitrite , reticulocyte , oxidative phosphorylation , methemoglobin , reactive nitrogen species , antioxidant , hemoglobin , enzyme , organic chemistry , nitrate , messenger rna , gene
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°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. Copyright © 2006 John Wiley & Sons, Ltd.