Possible mechanism of antioxidant action of dinitrosyl iron complexes

   
Shumaev K.B.1 , Kosmachevskaya O.V.2, Grachev D.I.3, Timoshin A.A.4, Topunov A.F.2, Lankin V.Z.4, Ruuge E.K.3

1. Research Center of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Moscow, Russia; National Medical Research Centre for Cardiology, Moscow, Russia
2. Research Center of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Moscow, Russia
3. National Medical Research Centre for Cardiology, Moscow, Russia; Lomonosov Moscow State University, Faculty of Physics, Moscow, Russia
4. National Medical Research Centre for Cardiology, Moscow, Russia
Section: Experimental Study
DOI: 10.18097/PBMC20216702162      PubMed Id: 33860774
Year: 2021  Volume: 67  Issue: 2  Pages: 162-168
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.
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Keywords: dinitrosyl iron complexes, nitric oxide, antioxidant effect, free radicals, peroxidation, low density lipoproteins
Citation:

Shumaev, K. B., Kosmachevskaya, O. V., Grachev, D. I., Timoshin, A. A., Topunov, A. F., Lankin, V. Z., Ruuge, E. K. (2021). Possible mechanism of antioxidant action of dinitrosyl iron complexes. Biomeditsinskaya Khimiya, 67(2), 162-168.
This paper is also available as the English translation: 10.1134/S1990750821040090
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