Protective Effect of Dinitrosyl Iron Complexes with Glutathione in Red Blood Cell Lysis Induced by Hypochlorous Acid.

Konstantin B. Shumaev,Daria V. Grigorieva,Olga V. Kosmachevskaya,Оleg M. Panasenko,Anatoly F. Vanin,Alexey F. Topunov,Maria S. Terekhova,Alexey V. Sokolov,Sergey N. Cherenkevich,Irina V. Gorudko,Enno K. Ruuge

doi:10.1155/2019/2798154

Abstract

Hypochlorous acid (HOCl), one of the major precursors of free radicals in body cells and tissues, is endowed with strong prooxidant activity. In living systems, dinitrosyl iron complexes (DNIC) with glutathione ligands play the role of nitric oxide donors and possess a broad range of biological activities. At micromolar concentrations, DNIC effectively inhibit HOCl-induced lysis of red blood cells (RBCs) and manifest an ability to scavenge alkoxyl and alkylperoxyl radicals generated in the reaction of HOCl with tert-butyl hydroperoxide. DNIC proved to be more effective cytoprotective agents and organic free radical scavengers in comparison with reduced glutathione (GSH). At the same time, the kinetics of HOCl-induced oxidation of glutathione ligands in DNIC is slower than in the case of GSH. HOCl-induced oxidative conversions of thiolate ligands cause modification of DNIC, which manifests itself in inclusion of other ligands. It is suggested that the strong inhibiting effect of DNIC with glutathione on HOCl-induced lysis of RBCs is determined by their antioxidant and regulatory properties.

Highlights

Hypochlorous acid (HOCl) (its salt is generally referred to as hypochlorite (OCl−)) is one of the main molecular precursors of free radicals in living organisms [1, 2]
The lysis of red blood cells (RBCs) under conditions of oxidative/halogenative stress was induced either by treatment of RBC suspensions with HOCl (the synthesis of the latter is catalyzed by myeloperoxidase (MPO)) or by adding MPO to RBC suspensions in the presence of its specific substrates (H2O2 and chloride)
After the treatment of RBCs with dinitrosyl iron complexes (DNIC), their resistance to HOCl increased considerably, while the rate of HOCl-induced lysis decreased with the increase in the DNIC concentration resulting in complete inhibition of RBC lysis at 50 μM DNIC (Figure 2(a))

Summary

Introduction

Hypochlorous acid (HOCl) (its salt is generally referred to as hypochlorite (OCl−)) is one of the main molecular precursors of free radicals in living organisms [1, 2]. Human red blood cells (RBCs) are widely used as a model for studying general mechanisms of cell injury under conditions of phagocyte-induced oxidative stress [3, 5,6,7]. A crucial role in stabilization and transport of NO to circulating blood is played by dinitrosyl iron complexes (DNIC) [18,19,20] The latter contain [Fe(NO)2] fragments able to bind to low-molecular thiols (e.g., glutathione and cysteine) or amino acid residues of proteins. The antioxidant and cytoprotective effects of DNIC on living cells and systems under conditions of oxidative stress [28,29,30,31,32,33] prompt a conclusion that in-depth study of DNIC effects on HOCl-induced lysis of RBСs is a task of paramount importance

Materials and Methods

Results

Discussion

60 Thioglo 1

Conclusions