Meconic acid is a possible neuroprotector: justification on in vitro experiments and its physico-chemical properties

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

Main representatives of gamma pyronic acid are meconic, comenic, chelidonic and kojic acid. It was found that comenic acid exerts a neuroprotective effect, and chelidonic acid has a pronounced anti-inflammatory effect. It was not studied whether meconic acid exhibits neuroprotective effects. The aim of this work was to assess the neuroprotective potential of meconic acid, taking into accout its physicochemical properties, using an in vitro model of ischemic stroke. Primary neuroglial culture was obtained from the cerebellum of 7-8-day-old Wistar rat pups by mechanical tissue dissociation. The protective effect of meconic acid on the culture of cerebellar neurons was studied using the model of glutamate toxicity and oxygen-glucose deprivation. Quantum mechanical calculations were used and experiments in the model system citrate-phosphate-luminol were conducted by the method of chemiluminescent analysis to investigate the antioxidant activity of meconic acid. The chelating properties of meconic acid with respect to Fe3+ in solutions were studied using Job's method. Meconic acid has been found to have a protective effect in in vitro models of ischemia. Its action leads to a decrease in the level of intracellular calcium and the restoration of the membrane potential of mitochondria in a culture of cerebellar neurons under glutamate exposure, resulting in an increase in the percentage of living cells under oxygen-glucose deprivation. Meconic acid has a high calculated antioxidant potential, confirmed experimentally. With an increase in the pH of the medium, stepwise binding of meconic acid with Fe3+ occurs with the formation of complexes with different ligand/metal ratios. At physiological pH, the composition of the resulting complex is 1:3. The obtained antioxidant, chelating, and cytoprotective action of meconic acid provides a basis for further study of the possible neuroprotective properties of this compound in in vivo experiments, and the data obtained in the work on its physicochemical properties can be useful for the synthesis and study of new coordination compounds based on meconic acid.

About the authors

S. V Kozin

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

L. I Ivashchenko

Kuban State University

Krasnodar, Russia

A. A Kravtsov

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

L. V Vasilyeva

Kuban State University

Krasnodar, Russia

A. M Vasiliev

Kuban State University

Krasnodar, Russia

N. N Bukov

Kuban State University

Krasnodar, Russia

A. A Dorohova

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Email: 013194@mail.ru
Krasnodar, Russia;Rostov-on-Don, Russia

O. M Lyasota

Kuban State University;Federal Research Center "Southern Scientific Center of the Russian Academy of Sciences"

Krasnodar, Russia;Rostov-on-Don, Russia

A. V Bespalov

Kuban State University

Krasnodar, Russia

References

  1. А. Я. Шурыгин, Препарат Бализ (Периодика Кубани, Краснодар, 2002).
  2. Л. В. Шурыгина, Э. И. Злищева и А. А. Кравцов, Эксперим. клинич. фармакология, 81 (4), 3 (2018).
  3. Л. В. Шурыгин, Э. И. Злищев, А. Н. Кравцова и др., Бюл. эксперим биологии и медицины, 163 (3), 325 (2017).
  4. А. А. Кравцов, А. Я. Шурыгин, Н. С. Скороход и др., Бюл. эксперим. биологии и медицины, 150 (10), 410 (2010).
  5. Л. В. Шурыгина, Э. И. Злищева и А. А. Кравцов, Бюл. эксперим. биологии и медицины, 165 (4), 457 (2018).
  6. Р. В. Кондратенко, А. Н. Чепкова, А. Я. Шурыгин и др., Бюл. эксперим. биологии и медицины, 136 (11), 523 (2003).
  7. D. S. Kim, S. J. Kim, M. C. Kim, et al., Biol. Pharm. Bull., 35 (5), 666 (2012).
  8. H. A. Oh, H. M. Kim, and H. J. Jeong, Int. Immunopharmacol., 11 (1), 39 (2011).
  9. И. В. Рогачевский, В. Б. Плахова, И. Н. Домнин и др., Клинич. патофизиология, 1, 15 (2006).
  10. Б. В. Крылов и др., Пат. РФ № 2322977 С1, Бюл. изобретений, № 12 (2008).
  11. N. N. Bukov, L. I. Ivashchenko, and V. T. Panyushkin, Rus. J. Gen. Chem., 91 (4) 1 (2021).
  12. O. V. Vetrovoy, E. A. Rybnikova, and M. O. Samoilov, Biochemistry, 82 (3), 392 (2017).
  13. L. Mezzaroba, D. F. Alfieri, and A. N. Colado Simão, Neurotoxicology 74, 230 (2019).
  14. J. Li, F. Cao, H.L. Yin, et al., Cell Death Dis., 11 (2), 88 (2020).
  15. P. Dusek, P. M. Roos, T. Litwin, et al., J. Trace Elements in Medicine and Biology, 31, 193 (2015).
  16. X. Wei, X. Yi, X. H. Zhu, et al., Oxidative Medicine and Cellular Longevity, 2020, 1 (2020).
  17. R. J. Ward, D. T. Dexter, A. Martin-Bastida, et al., Int. J. Mol. Sci., 22 (7), 3338 (2021).
  18. S. Entezari, S. M. Haghi, N. Norouzkhani, et al., J. Toxicol., 2022, 1 (2022).
  19. I. A. Mulder, E. T. van Bavel, H. E. de Vries, et al., Fluids and Barriers of the CNS, 18 (1), 46 (2021).
  20. B. Bargagna, L. Ciccone, S. Nencetti, et al., Molecules, 26 (19), 6015 (2021).
  21. S. Paul and E. Candelario-Jalil, Exp. Neurol., 335, 1 (2021).
  22. С. В. Козин, А. А. Кравцов, С. В. Кравченко и др., Бюл. эксперим. биологии и медицины, 171 (5), 592 (2021).
  23. P. Güntzel, L. Forster, C. Schollmayer, et al., Org. Prepar. Procedures Int., 50 (5), 512 (2018).
  24. I. A. Antipova, S. A. Mukha, and S. A. Medvedeva, Rus. Chem. Bull., 53 (4), 780 (2004).
  25. Л. В. Шурыгина, А. А. Кравцов, С. В. Козин и др., Растительные ресурсы, 53 (2), 291 (2017).
  26. F. Neese, WIREs Comput. Mol. Sci., 2, 73 (2011).
  27. A. D. Becke, Phys. Rev. A, 38, 3098 (1988).
  28. S. Grimme, S. Ehrlich, and L. Goerigk, J. Comput. Chem., 32, 1456 (2011).
  29. F. Weigend and R. Ahlrichs, Phys. Chem. Chem. Phys., 7, 3297 (2005).
  30. J. Tomasi, B. Mennucci, and R. Cammi, Chem. Rev., 105, 2999 (2005).
  31. С. В. Козин, А. А. Кравцов, А. А. Елкина и др., Биофизика, 64 (2), 362 (2019).
  32. A. Kravtsov, S. Kozin, A. Basov, et al., Molecules, 27 (1), 243 (2022).
  33. S. Anitha, S. Krishnan, K. Senthilkumar, et al., Mol. Physics, 118, 17 (2020).
  34. J. Rimarcik, V. Lukes, E. Klein, et al., J. Mol. Struct.: THEOCHEM, 952, 25 (2010).
  35. V. M. Nurchi, G. Crisponi, J. I. Lachowicz, et al., J, Inorg. Biochem., 104 (5), 560 (2010).
  36. E. P. Raven, P. H. Lu, T. A. Tishler, et al., J. Alzheimer's Dis., 37 (1), 127 (2013).
  37. B. Do Van, F. Gouel, A. Jonneaux, et al., Neurobiol. Dis., 94, 169 (2016).
  38. J. J. Zhang, J. Du, N. Kong, et al., Ann. Translat. Med., 9 (19), 1503 (2021).
  39. X. L. Fang, S. Y. Ding, X. Z. Du, et al., Front. Neurol., 13 (2022).
  40. O. Y. Selyutina, P. A. Kononova, V. E. Koshman, et al., Antioxidants (Basel), 11 (2), 376 (2022).
  41. S. Satarker, S. L. Bojja, P. C. Gurram, et al., Cells, 11 (7), 1139 (2022).
  42. A. Scimemi, J. S. Meabon, R. L. Woltjer, et al., J. Neurosci., 33 (12), 5312 (2013).
  43. S. Garofalo, G. Cocozza, G. Bernardini, et al., Brain, Behavior, and Immunity, 105, 1 (2022).
  44. Z. Shen, M. Xiang, C. Chen, et al., Biomed. Pharmacother., 151 (2022).
  45. A. Jurcau and A. I. Ardelean, Biomedicines, 10 (3), 574 (2022).
  46. M. Regulska, M. Szuster-Głuszczak, E. Trojan, et al., Curr. Neuropharmacol., 19 (2), 278 (2021).
  47. M. Verma, B. N. Lizama, and C. T. Chu, Translat. Neurodegeneration., 11 (1), 3 (2022).
  48. A. A. Khrapov, A. N. Chepkova, A. Y. Shurygin, et al., Bull. Exp. Biol. Med., 125 (1), 53 (1998).

Copyright (c) 2023 Russian Academy of Sciences

This website uses cookies

You consent to our cookies if you continue to use our website.

About Cookies