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A Possible Mechanism of the Antioxidant Action of Dinitrosyl Iron Complexes

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Biochemistry (Moscow), Supplement Series B: Biomedical Chemistry Aims and scope Submit manuscript

Abstract—

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.

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ACKNOWLEDGMENTS

The authors are grateful to M.A. Grechnikova, I.S. Pugachenko and Dr. G.G. Konovalova for their help in carrying out some experiments.

Funding

This work was partially supported by the Russian Foundation for Basic Research (project no. 19-015-00444).

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Authors and Affiliations

  1. Research Center of Biotechnology of the Russian Academy of Sciences, Bach Institute of Biochemistry, Leninskii prospect 33, bldg. 2., 119071, Moscow, Russia

    K. B. Shumaev, O. V. Kosmachevskaya & A. F. Topunov

  2. National Medical Research Centre for Cardiology, 3-rd Cherepkovskaya 15a, 121552, Moscow, Russia

    K. B. Shumaev, D. I. Grachev, A. A. Timoshin, V. Z. Lankin & E. K. Ruuge

  3. Moscow State University, Faculty of Physics, Leninskie Gory1/2, 119991, Moscow, Russia

    D. I. Grachev & E. K. Ruuge

Authors
  1. K. B. Shumaev
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  2. O. V. Kosmachevskaya
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  3. D. I. Grachev
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  4. A. A. Timoshin
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  6. V. Z. Lankin
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Corresponding author

Correspondence to K. B. Shumaev.

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COMPLIANCE WITH ETHICAL STANDARDS

The study was carried out in accordance with the Declaration of Helsinki of the World Medical Association and approved by the Ethics Committee of the National Medical Research Center for Cardiology (meeting protocol no. 177 of September 7, 2012 and no. 221 of November 28, 2016). Donors of the blood used to obtain LDL gave their voluntary informed consent to participate in the study. In other experiments, biomaterials obtained from humans and animals were not used.

CONFLICT OF INTEREST

The authors declare that they have no conflict of interest.

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Translated by A. Medvedev

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Shumaev, K.B., Kosmachevskaya, O.V., Grachev, D.I. et al. A Possible Mechanism of the Antioxidant Action of Dinitrosyl Iron Complexes. Biochem. Moscow Suppl. Ser. B 15, 313–319 (2021). https://doi.org/10.1134/S1990750821040090

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