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Antioxidant properties of 3-hydroxy-2-ethyl-6-methylpyridinium nitroxysuccinate upon the activation of oxidative processes by antitumor drug Cisplatin in vitro and in vivo

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Abstract

It was determined in experiments in vitro that 3-hydroxy-2-ethyl-6-methylpyridinium nitroxysuccinate (1) significantly decreased the formation of reactive oxygen species under the action of Cisplatin in normal cells and did not affect this process in tumor cells. The effect of Cisplatin on the cardiovascular system of animals was accompanied by a significant increase in the concentration of the oxidative stress marker malondialdehyde (MDA) in the blood and heart, as well as an increase in expression of GCLM, GPX1, and NQO1 genes of the antioxidant system (AOS) in heart tissues. The administration of compound 1 in combination with Cisplatin decreased the MDA concentration in the blood and heart to a higher extent than the administration of Cisplatin only. A combination of compound 1 with Cisplatin caused an increase in gene expression of glutathione AOS genes (similarly to the action of Cisplatin applied as monotherapy) and, in addition, a twofold increase in gene expression of NAD(P)H:quinone oxidoreductase. New compound 1 is shown to be able to exhibit antioxidant properties in vitro and in vivo by decreasing the accumulation of reactive oxygen species, suppression of lipid peroxidation processes, and activation of gene expression of the antioxidant system. The data obtained show that this compound is promising for decreasing side effects of the anticancer drug Cisplatin.

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Authors and Affiliations

  1. Institute of Problems of Chemical Physics, Russian Academy of Sciences, 1 prosp. Akademika Semenova, 142432, Chernogolovka, Moscow Region, Russian Federation

    T. R. Prikhodchenko, A. A. Balakina, V. I. Amozova, S. Ya. Gadomsky & D. V. Mishchenko

  2. Scientific Educational Center in Chernogolovka, Moscow Region State University, 24 ul. Very Voloshinoi, 141014, Mytishchi, Moscow Region, Russian Federation

    D. V. Mishchenko

  3. Department of Fundamental Physical and Chemical Engineering, Lomonosov Moscow State University, 1 Leninskie Gory, 119991, Moscow, Russian Federation

    D. V. Mishchenko

Authors
  1. T. R. Prikhodchenko
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  2. A. A. Balakina
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  3. V. I. Amozova
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  4. S. Ya. Gadomsky
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  5. D. V. Mishchenko
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Corresponding author

Correspondence to A. A. Balakina.

Additional information

Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2629–2635, December, 2022.

This work was financially supported by the Ministry of Science and Higher Education of the Russian Federation (Project Nos AAAA-A19-119092390041-5 and AAAA-A19-119071890015-6).

All experiments involving animals and their keeping corresponding to the rules established by the Bioethical Commission of the Institute of Problems of Chemical Physics of the Russian Academy of Sciences (protocol of June 21, 2021 No. 6/21) and The European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes.

The authors declare no competing interests.

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Prikhodchenko, T.R., Balakina, A.A., Amozova, V.I. et al. Antioxidant properties of 3-hydroxy-2-ethyl-6-methylpyridinium nitroxysuccinate upon the activation of oxidative processes by antitumor drug Cisplatin in vitro and in vivo. Russ Chem Bull 71, 2629–2635 (2022). https://doi.org/10.1007/s11172-022-3692-y

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  • DOI: https://doi.org/10.1007/s11172-022-3692-y

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