A Possible Mechanism of the Antioxidant Action of Dinitrosyl Iron Complexes

The antioxidant effect of dinitrosyl iron complexes (DNICs) was studied in various model systems. DNICs with glutathione ligand (DNIC-GS) 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, DNIC-GS suppressed reactive oxygen species (ROS) formation during co-oxidation of lecithin liposomes and glucose. Free radical oxidation in this system was induced with a lipophilic azo initiator (AIBN) 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. DNIC-GS scavenged 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 mode of the antiradical effect DNIC-GS; moreover, these complexes were more efficient than GSH. EPR spectra of adducts of the DEPMPO spin trap with free radicals suggest that the interaction of DNIC-GS and superoxide does not result in the formation of the thiyl radical of glutathione. Here we propose a mechanism of the antioxidant action of DNIC-GS, suggesting that unstable intermediate complexes are formed upon their interaction with superoxide or lipid radicals. After subsequent intramolecular rearrangement, these intermediates decompose without the free radical formation as the by-products.