Advertisement

Acetylcholinesterase Inhibitor Paraoxon Intensifies Oxidative Stress Induced in Rat Erythrocytes In Vitro

  • I. V. Mindukshev
  • E. A. Skverchinskaya
  • D. A. Khmelevskoy
  • I. A. Dobrylko
  • N. V. GoncharovEmail author
ARTICLES

Abstract

Isoform H of acetylcholinesterase (AChE) is located on the outer surface of erythrocytes; its inhibition with organophosphorus compounds (OPC) may impair structural and functional properties of erythrocytes. The aim of this study was to elucidate the effects of paraoxon (POX) on the osmotic resistance, the level of reactive oxygen species (ROS), intracellular esterase activity, and externalization of phosphatidylserine in rat erythrocytes under oxidative stress induced by tert-butyl hydroperoxide (tBH). It has been found that POX did not affect the level of ROS and the activity of intracellular esterases; however, under conditions of induced oxidative stress, it potentiated the effects associated with impairment of the erythrocyte deformation characteristics and provoked cell death associated with externalization of phosphatidylserine. The effects of POX were not caused by the solvent DMSO and were observed only in the calcium containing medium. The results obtained with the in vitro model on the combined effects of the primary specific and secondary nonspecific factors on erythrocytes may be of help in the development or improvement of combined therapeutics for acute poisonings and the prevention of their consequences.

Keywords:

erythrocytes acetylcholinesterase organophosphates oxidative stress 

Notes

ACKNOWLEDGMENTS

Experiments on the Navios flow cytometer have been conducted in the SUC of the IEPB RAS. The work was supported by the Russian Science Foundation (project no. 16-15-00199).

COMPLIANCE WITH ETHICAL STANDARDS

Conflict of interests. The authors declare that they have no conflict of interest.

Statement on the welfare of animals. All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.

REFERENCES

  1. 1.
    Daniels G. 2007. Functions of red cell surface proteins. Vox Sang. 93 (4), 331–340.CrossRefGoogle Scholar
  2. 2.
    Officioso A., Manna C., Alzoubi K., Lang F. 2016. Bromfenvinphos induced suicidal death of human erythrocytes. Pestic Biochem. Physiol. 126, 58–63.CrossRefGoogle Scholar
  3. 3.
    Szatkowska B., Bukowska B., Huras B. 2011. The effect of bromfenvinphos and its impurities on human erythrocyte. Food Chem. Toxicol. 49 (2), 502–507.CrossRefGoogle Scholar
  4. 4.
    Sosnowska B., Huras B., Bukowska B. 2015. Oxidative stress in human erythrocytes treated with bromfenvinphos and its impurities. Pestic Biochem. Physiol. 118, 43–49.CrossRefGoogle Scholar
  5. 5.
    Santos N.C., Figueira-Coelho J., Saldanha C., Martins-Silva J. 2002. Biochemical, biophysical and haemorheological effects of dimethylsulphoxide on human erythrocyte calcium loading. Cell Calcium. 31 (4), 183–188.CrossRefGoogle Scholar
  6. 6.
    Goncharov N.V., Prokofieva D.S., Voitenko N.G., Babakov V.N., Glashkina L.M. 2010. Molecular mechanisms of cholinergic regulation and dysregulation. Toksikol. vestnik (Rus.). 2, 5–10.Google Scholar
  7. 7.
    Nadeev, A.D., Zinchenko V.P., Avdonin, P.V., Goncharov N.V. 2014. Toxic and signaling effects of reactive oxygen species. Toksikologicheskiy vestnik (Rus.). 2, 22–27.Google Scholar
  8. 8.
    Mandal D., Moitra P.K., Saha S., Basu J. 2002. Caspase 3 regulates phosphatidylserine externalization and phagocytosis of oxidatively stressed erythrocytes. FEBS Lett. 513 (2–3), 184–188.CrossRefGoogle Scholar
  9. 9.
    Iuchi Y. 2012. Anemia caused by oxidative stress, anemia. Dr. Donald Silverberg (Ed.), InTech, Available from: http://www.intechopen.com/books/anemia/anemia-caused-byoxidative-stress.Google Scholar
  10. 10.
    Mindukshev I.V., Roukoyatkina N.I., Dobrilko I.A., Skwirczynskaya E.A., Nikitina E.R., Krivoshlyk V.V., Gambaryan S.P., Krivchenko A.I. 2013. Features of apoptosis of nuclear-free cells: Platelets and erythrocytes. Ross. Fisiol. zhurnal (Rus.). 99 (1), 92–110.Google Scholar
  11. 11.
    Walski T., Chludzińska L., Komorowska M., Witkiewicz W. 2014. Individual osmotic fragility distribution: A new parameter for determination of the osmotic properties of human red blood cells. Biomed. Res. Int. doi  https://doi.org/10.1155/2014/162102
  12. 12.
    Benesch R.E., Benesch R., Yung S. 1973. Equations for the spectrophotometric analysis of hemoglobin mixtures. Anal. Biochem. 55, 245–248.CrossRefGoogle Scholar
  13. 13.
    Mindukshev I.V., Krivoshlyk V.V., Dobrilko I.A., Goncharov N.V. Vivulenets E.V., Kuznetsov S.V., Krivchenko A.I. 2010. Violation of deformation and transport characteristics of erythrocytes in the development of apoptosis. Biol. membrany (Rus.). 27 (1), 28–38.Google Scholar
  14. 14.
    Mindukshev I.V., Senchenkova E.Y., Goncharov N.V., Vivulanets E.V., Krivoshlyk V.V. 2010. New methods for studying platelets and red blood cells, based upon the low-angle light scattering technique. In: Hemorheology: Blood Flow, Disturbance and Prognosis. Ed. F. Columbus, N.Y.: Nova Sci. Publ., p. 87–124.Google Scholar
  15. 15.
    Skverchynskaya E.A., Nikitina E.R., Sudnitsyna J.S., Krivchenko A.I., Gambaryan, S.P., Mindukshev I.V. 2015. Hemolysis of erythrocytes or formation of microparticles in apoptosis under oxidative stress? In: Receptors and intracellular signaling (Rus). 2, 564–569. https:// elibrary.ru/item.asp?id=28974843, https://elibrary.ru/ item.asp?id=29279171.Google Scholar
  16. 16.
    Spring F.A., Gardner B., Anstee D.J. 1992. Evidence that the antigens of the Yt blood group system are located on human erythrocyte acetylcholinesterase. Blood. 80 (8), 2136–2141.Google Scholar
  17. 17.
    Wessler I., Kirkpatrick C.J., Racké K. 1999. The cholinergic ‘pitfall’: Acetylcholine, a universal cell molecule in biological systems, including humans. Clin. Exp. Pharmacol. Physiol. 26 (3), 198–205.CrossRefGoogle Scholar
  18. 18.
    Wessler I., Kilbinger H., Bittinger F., Unger R., Kirkpatrick C.J. 2003. The non-neuronal cholinergic system in humans: Expression, function and pathophysiology. Life Sci. 72 (18–19), 2055–2061.CrossRefGoogle Scholar
  19. 19.
    Carvalho F.A., Mesquita R., Martins-Silva J., Saldanha C. 2004. Acetylcholine and choline effects on erythrocyte nitrite and nitrate levels. J. App.l Toxicol. 24 (6), 419–427.CrossRefGoogle Scholar
  20. 20.
    Carvalho F.A., Almeida J.P., Fernandes I.O., Freitas-Santos T., Saldanha C. 2008. Non-neuronal cholinergic system and signal transduction pathways mediated by band 3 in red blood cells. Clin. Hemorheol. Microcirc. 40 (3), 207–227.Google Scholar
  21. 21.
    Teixeira P., Duro N., Napoleão P., Saldanha C. 2015. Acetylcholinesterase conformational states influence nitric oxide mobilization in the erythrocyte. J. Membr. Biol. 248 (2), 349–354.CrossRefGoogle Scholar
  22. 22.
    Prall Y.G., Gambhir K.K., Ampy F.R. 1998. Acetylcholinesterase: An enzymatic marker of human red blood cell aging. Life Sci. 63 (3), 177–184.CrossRefGoogle Scholar
  23. 23.
    Shmurak, V.I., Kurdyukov, I.D., Nadeev A.D., Voitenko N.G., Glaskina L.M., Goncharov N.V. 2012. Biochemical markers of intoxication with organophosphorus toxic substances. Toksikol. vestnik (Rus.). 4, 30–34.Google Scholar
  24. 24.
    Hundekari I.A., Suryakar A.N., Rathi D.B. 2013. Acute organophosphorus pesticide poisoning in North Karnataka, India: Oxidative damage, haemoglobin level and total leukocyte. Afr. Health Sci. 13 (1), 129–136.Google Scholar
  25. 25.
    Mindukshev I.V., Krivoshlyk V.V., Ermolaeva E.E., Dobrylko I.A., Senchenkov E.V., Goncharov N.V., Jenkins R.O., Krivchenko A.I. 2007. Necrotic and apoptotic volume changes of erythrocytes investigated by low-angle light scattering technique. Spectroscopy Int. J. 21 (2), 105–120.CrossRefGoogle Scholar
  26. 26.
    Zipser Y., Piade A., Barbul A., Korenstein R., Kosower N.S. 2002. Ca2+ promotes erythrocyte band 3 tyrosine phosphorylation via dissociation of phosphotyrosine phosphatase from band 3. Biochem. J. 368 (1), 137–144.CrossRefGoogle Scholar
  27. 27.
    Shaik N., Lupescu A., Lang F. 2012. Sunitinib-sensitive suicidal erythrocyte death. Cell Physiol. Biochem. 30 (3), 512–522.CrossRefGoogle Scholar
  28. 28.
    Bogdanova A., Makhro A., Wang J., Lipp P., Kaestner L. 2013. Calcium in red blood cells–a perilous balance. Int. J. Mol. Sci. 14 (5), 9848–9872.CrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2019

Authors and Affiliations

  • I. V. Mindukshev
    • 1
  • E. A. Skverchinskaya
    • 1
  • D. A. Khmelevskoy
    • 1
  • I. A. Dobrylko
    • 1
  • N. V. Goncharov
    • 1
    • 2
    Email author
  1. 1.Sechenov Institute of Evolutionary Physiology and Biochemistry, Russian Academy of SciencesSt. PetersburgRussia
  2. 2.Research Institute of Hygiene, Occupational Pathology and Human Ecologyp/o KuzmolovskyRussia

Personalised recommendations