Possible mechanism of antioxidant action of dinitrosyl iron complexes

Abstract

The antioxidant effect of dinitrosyl iron complexes (DNICs) was studied in various model systems. DNICs with glutathione ligands effectively inhibited Cu2+-induced peroxidation of low density lipoproteins (LDL). The antioxidant effect of DNICs with phosphate ligands and free reduced glutathione (GSH) was less pronounced. In addition, DNICs with glutathione suppressed the formation of reactive oxygen species during co-oxidation of lecithin liposomes and glucose. Free radical oxidation in this system was induced with a lipophilic azo initiator and evaluated by luminol-dependent chemiluminescence. NO sharply stimulated chemiluminescence during co-oxidation of glucose and liposomes, thus suggesting the formation of potent oxidants under these conditions. Glutathione DNICs scavenge the superoxide radical anion generated in the xanthine-xanthine oxidase system. Superoxide production was assessed by lucigenin-dependent chemiluminescence and electron paramagnetic resonance (EPR) spectroscopy. Chemiluminescence revealed the dose-dependent character of antiradical effect of glutathione DNICs; moreover, these complexes turned out to be more efficient than GSH. EPR spectra of the adducts of the DEPMPO spin trap with free radicals suggest that the interaction of glutathione DNICs and superoxide does not result in the formation of the thiyl radical of glutathione. Here we propose a mechanism of the antioxidant action of glutathione DNICs, suggesting that unstable intermediate complexes are formed upon their interaction with superoxide or lipid radicals. Further, as a result of intramolecular rearrangement, these intermediates decompose without the free radical as the by-products.

Histidine-Bound Dinitrosyl Iron Complexes: Antioxidant and Antiradical Properties

“…Likewise, in the presence of BSA-DNICs, the chemiluminescence light sum was two times lower than that in the sample with albumin (Figure 6B, columns 1 and 2). In addition, the kinetic chemiluminescence curve of the samples with BSA-DNICs had an induction period characteristic of many antioxidants [9,60]. These results indicate that BSA-DNICs effectively neutralized the pro-oxidants formed.…”

“…•− or lipid radicals, DNICs are transformed into intermediates and further disintegrated without forming strong oxidants. These intermediates may be iron complexes containing bound peroxynitrite or alkyl derivatives of peroxynitrite (LOONO) [9]. This complex containing ONOO was obtained via the interaction of molecular oxygen with DNICs liganded by synthetic nitrogen-containing compounds [69].…”

“…Physiological derivatives of nitric oxide (NO • ) including dinitrosyl iron complexes (DNICs) perform numerous functions in living systems [1][2][3][4]. DNICs have a wide range of biological activities: they participate in NO • scavenging, have hypotensive, cytoprotective, and antioxidant properties, inhibit platelet aggregation, increase the elasticity of erythrocyte membranes, and promote wound healing [3,[5][6][7][8][9][10]. Most of these activities are related to the ability of DNICs to act as NO • donors.…”

The Relationship of Glutathione-S-Transferase and Multi-Drug Resistance-Related Protein 1 in Nitric Oxide (NO) Transport and Storage

“…With respect to the effect of DNICs on cellular redox status, free DNICs have been shown to disrupt the cellular redox environment by irreversibly inhibiting glutathione reductase [140,156], which could lead to a more oxidized micro-environment. In contrast, the possible antioxidant functions of DNICs were demonstrated by their ability to inhibit Cu +2 -induced peroxidation of low-density lipoprotein (LDL) and prevent ROS generation during co-oxidation of lecithin-containing liposomes and glucose [170]. Another antioxidant mechanism was proposed by Shumaev et al [171], who demonstrated that DNICs reduce oxoferryl-myoglobin more efficiently than S-nitrosoglutathione and GSH.…”