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Effective inhibition of copper-catalyzed production of hydroxyl radicals by deferiprone

  • V. A. Timoshnikov
  • T. Kobzeva
  • O. Y. Selyutina
  • N. E. PolyakovEmail author
  • G. J. Kontoghiorghes
Original Paper
  • 42 Downloads

Abstract

Copper ions can catalyze the production of free oxygen radicals (•OH and •OOH) similar to iron ions. The capacity to initiate oxidative damage is most commonly attributed to Cu-induced toxicity in copper-related diseases where there is an increase in copper levels and also when Cu homeostasis and regulation are disrupted. An antioxidant/chelator inhibiting Cu-induced oxidative damage could play a significant role in the treatment of such Cu-related diseases. Deferiprone has high affinity for copper binding and can be considered for the potential treatment of copper toxicity and overloading conditions, such as Wilson’s disease. In the present study, the ability of deferiprone to inhibit the production of hydroxyl radicals catalyzed by copper ions was elucidated using an Electron Paramagnetic Resonance (EPR) spin trapping technique. The values of g-factors and hyperfine splitting constants were calculated for Cu(II)-deferiprone 1:1 complex: (a = 58.5 G, g = 2.1667) and 1:2 complex: (a = 73.0 G, g = 2.1378). The TMIO spin trap (2,2,4-trimethyl-2H-imidazole-1-oxide) was used for the detection of free radicals formed in Fenton-like copper-catalyzed reactions. It was demonstrated that the interaction of deferiprone with Cu2+ ions completely inhibited hydroxyl radical (•OH) production in the presence of hydrogen peroxide. It was found also that deferiprone inhibits Cu-induced oxidation of linoleic acid in micellar solution. In addition to existing data for water solutions, the affinity of deferiprone for copper binding in non-aqueous environment has been elucidated.

Keywords

Deferiprone Copper chelation Copper toxicity Hydroxyl radical EPR 

Notes

Acknowledgements

This research was supported by grant from Russian Foundation for Basic Research No 18-34-00343. The reported research was also funded by Russian Ministry of Science and Education (State assignments No 0304-2017-0009). Special thanks to Dr. Igor Kirilyuk (Novosibirsk Institute of Organic Chemistry, Russia) and Dr. Irina Slepneva (Institute of Chemical Kinetics and Combustion, Russia) for the samples of spin traps.

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Copyright information

© Society for Biological Inorganic Chemistry (SBIC) 2019

Authors and Affiliations

  • V. A. Timoshnikov
    • 1
    • 2
  • T. Kobzeva
    • 1
  • O. Y. Selyutina
    • 1
  • N. E. Polyakov
    • 1
    Email author
  • G. J. Kontoghiorghes
    • 3
  1. 1.V. A. Institute of Chemical Kinetics and CombustionNovosibirskRussia
  2. 2.Novosibirsk State UniversityNovosibirskRussia
  3. 3.Postgraduate Research Institute of Science, Technology, Environment and MedicineLimassolCyprus

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