Metabolizam SIN-1 (donor peroksinitrita) u crvenim krvnim ćelijama pacova
Metabolism of SIN-1: Peroxynitrite donor in rat red blood cells
Štajn, Andraš Š.
Maletić, Snežana D.
Ognjanović, Branka I.
Radojičić, Ratko M.
Article (Published version)
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The aim of this study is elucidation of the molecular mechanism of the 3-morpholino-sydnonimine-hydrochloride (SIN-1) action, particularly its metabolism in rat erythrocytes and reticulocytes. SIN-1 is active metabolite of molsidomine, an established vasodilator drug, clinically used in the treatment of coronary artery disease. Rats erythrocyte and reticulocyte-rich suspensions were aerobically incubated without (control) or in the presence of SIN-1 (0.1, 0.25, 0.5, 1,0 and 1.5 mM). The concentrations of reactive nitrogen species (RNS), reactive oxygen species (ROS) and parameters that indicate oxidative damage of red blood cells were determined after incubation. In rat erythrocytes SIN-1 in high doses increased concentrations of nitrite (NO+ ion indicator), hydroxylamine (NO- ion indicator) and 3-nitrotyrosine (peroxynitrite indicator). Concentration of superoxide anion radical (O2) increased in the presence of SIN-1 on dose-dependent way (except in the presence of higher applied dose), while level of hydrogen peroxide (H2O2) did not alter. In rat reticulocytes SIN-1 significantly increased 3-nitrotyrosine concentrations only. In addition, low doses of SIN-1 induced decrease of O2.- level, while concentration of H2O2 increased dose-dependently. These data indicate that SIN-1-induced nitrosative and oxidative stress in rat red blood cells. The strong oxidative damage of erythrocytes and reticulocytes (increased level of methemoglobin, Heinz bodies and lipid peroxides concentrations) are appeared as consequence of SIN-1-induced oxidative stress.