Genotoxic effect of selenium arabinogalactan nanocomposite on nucleated blood cells

Introduction. Selenium (Se) nanoparticles have attracted the interest of researchers for various applications due to their unusual properties. Despite their advantages, Se nanoparticles also have toxic effects, so for their successful use it is necessary to know the doses that are safe for the use. An important component in the development of pathological processes is the occurrence of DNA damage after exposure to Se nanoparticles, which can lead to severe disorders.

Materials and methods. Male white rats were orally administered a solution of Se nanocomposite at a dose of 500 µg/kg for 10 days. The genotoxicity of the nanocomposite under study was assessed by the occurrence of DNA damage in blood cells using the DNA comet method in the alkaline version. The results were obtained during 2 stages: one day after exposure and after 4 months to identify the persistence or absence of a negative effect.

Results. With using the DNA comet method, intragastric administration of Se nanocomposite was found to cause the damage to the DNA structure, and this effect persists not only 24 hours after exposure, but also 4 months later.

Limitations. The study is limited to the study of DNA fragmentation on the next day after a 10-day exposure to Se nanocomposite in male white rats and during the long-term period after 4 months.

Conclusion. The study revealed persistent DNA damage in the nucleated blood cells of male albino rats, which apparently may be associated with the main mechanism of Se toxicity: nonspecific replacement of sulfur in sulfur-containing amino acids. However, the toxic effects of the nanocomposite may also be caused by its pro-oxidant properties, which requires further confirmation.

Compliance with ethical standards. The study was approved by the local Ethics Committee of the East-Siberian Institute of Medical and Ecological Research (Protocol No.1 of 12/18/2017), conducted in accordance with the European Convention for the Protection of Vertebrates Used for Experiments or Other Scientific Purposes (ETS N 123), directive of the European Parliament and the Council Of the European Union 2010/63/EC of 22.09.2010 on the protection of animals used for scientific purposes.

Contribution:
Tyutrina V.A. — literature search, experiment, writing, statistical processing, article design;
Sosedova L.M. — concept, writing, discussion of relevance and results;
Titov E.A. — concept, experiment.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Conflict of interest. The authors declare no conflict of interest.

Acknowledgment. The work was carried out according to the research plan within the framework of the state task.

Received: March 13, 2024 / Revised: April 8, 2024 / Accepted: June 19, 2024 / Published: July 17, 2024

1. Kieliszek M. Selenium-fascinating microelement, properties and sources in food. Molecules. 2019; 24(7): 1298. https://doi.org/10.3390/molecules24071298

2. Söderlund M., Virkanen J., Holgersson S., Lehto J. Sorption and speciation of selenium in boreal forest soil. J. Environ. Radioactiv. 2016; (164): 220–31. https://doi.org/10.1016/j.jenvrad.2016.08.006

3. Kul’chitskii N.A., Naumov A.V. Modern state of markets of selenium and selenium-based compounds. Izvestiya vysshikh uchebnykh zavedenii. Tsvetnaya metallurgiya. 2015; (3): 40–8. https://doi.org/10.17073/0021-3438-2015-3-40-48 https://elibrary.ru/tyjwwx (in Russian)

4. Mercan Y.U., Başbuğan Y., Uyar A., Kömüroğlu A.U., Keleş Ö.F. Use of an antiarrhythmic drug against acute selenium toxicity. J. Trace Elem. Med. Biol. 2020; 59: 126471. https://doi.org/10.1016/j.jtemb.2020.126471

5. Holness D.L., Taraschuk I.G., Nethercott J.R. Health status of copper refinery workers with specific reference to selenium exposure. Arch. Environ. Health. 1989; 44(5): 291–7. https://doi.org/10.1080/00039896.1989.9935896

6. Kinnigkiet G. Investigation of workers exposed to selenium in a factory producing rectifiers. Bull. Hyg. 1962; (37): 1029–39.

7. Diskin C.J., Tomasso C.L., Alper J.C., Glaser M.L., Fliegel S.E. Long-term selenium exposure. Arch. Intern. Med. 1979; 139(7): 824–6.

8. Brune D., Nordberg G., Wester P.O. Distribution of 23 elements in the kidney, liver and lungs of workers from a smeltery and refinery in North Sweden exposed to a number of elements and of a control group. Sci. Total. Environ. 1980; 16(1): 13–35. https://doi.org/10.1016/0048-9697(80)90100-x

9. Measurement of Concentrations of Harmful Substances in the Air of the Working Area: Guidelines. Issue 41 [Izmerenie kontsentratsii vrednykh veshchestv v vozdukhe rabochei zony: Metodicheskie ukazaniya]. Moscow; 2006. (in Russian)

10. Encinar J.R., Śliwka-Kaszyńska M., Polatajko A., Vacchina V., Szpunar J. Methodological advances for selenium speciation analysis in yeast. Anal. Chim. Acta. 2003; 500(1): 171–83. https://doi.org/10.1016/S0003-2670(03)00754-2

11. Tapiero H., Townsend D.M., Tew K.D. The antioxidant role of selenium and seleno-compounds. Biomed. Pharmacother. 2003; 57(3–4): 134–44. https://doi.org/10.1016/s0753-3322(03)00035-0

12. Frączek A., Pasternak K. Selenium in medicine and treatment. J. Elem. 2013; 18(1): 145–63. https://doi.org/10.5601/jelem.2013.18.1.13

13. Kieliszek M., Błażejak S. Selenium: Significance, and outlook for supplementation. Nutrition. 2013; 29(5): 713–8. https://doi.org/10.1016/j.nut.2012.11.012

14. Ivanenko N.V. Environmental Toxicology [Ekologicheskaya toksikologiya]. Vladivostok; 2006. (in Russian)

15. Kieliszek M., Błażejak S. Current knowledge on the importance of selenium in food for living organisms: A review. Molecules. 2016; 21(5): 609. https://doi.org/10.3390/molecules21050609

16. Nuttal K.L. Evaluating selenium poisoning. Ann. Clin. Lab. Sci. 2006; 36(4): 409–20.

17. Urbankova L., Skalickova S., Pribilova M., Ridoskova A., Pelcova P., Skladanka J., et al. Effects of sub-lethal doses of selenium nanoparticles on the health status of rats. Toxics. 2021; 9(2): 28. https://doi.org/10.3390/toxics9020028

18. Wadhwani S.A., Shedbalkar U.U., Singh R., Chopade B.A. Biogenic selenium nanoparticles: Current status and future prospects. Appl. Microbiol. Biotechnol. 2016; 100(6): 2555–66. https://doi.org/10.1007/s00253-016-7300-7

19. Sun F., Wang J., Wu X., Yang C.S., Zhang J. Selenium nanoparticles act as an intestinal p53 inhibitor mitigating chemotherapy-induced diarrhea in mice. Pharmacol. Res. 2019; 149: 104475. https://doi.org/10.1016/j.phrs.2019.104475

20. Sosedova L.M., Rukavishnikov V.S., Sukhov B.G., Borovskii G.B., Titov E.A., Novikov M.A., et al. Synthesis of chalcogen-containing nanocomposites of selenium and tellurium with arabinogalactan and a study of their toxic and antimicrobial properties. Rossiiskie nanotekhnologii. 2018; 13(5–6): 290–294. https://doi.org/10.1134/S1995078018030175 https://elibrary.ru/yohdkh (in Russian)

21. Titov E.A., Rukavishnikov V.S., Sosedova L.M., Novikov M.A., Buinova E.V. Morphofunctional changes in the tissue of the brain, liver and kidneys of white rats under the influence of selenium nanocomposite encapsulated in the polymer matrix of arabinogalactan. Acta biomedica scientifica. 2021; 6(5): 92–9. https://doi.org/10.29413/ABS.2021-6.5.9 https://elibrary.ru/antutb (in Russian)

22. Durnev A.D., Zhanataev A.K., Anisina E.A., Sidneva E.S., Nikitina V.A., Oganesyants L.A., et al. The Use of the Method of Alkaline Gel-Electrophoresis of Isolated Cells to Assess the Genotoxic Properties of Natural and Synthetic Compounds [Primenenie metoda shchelochnogo gel’-elektroforeza izolirovannykh kletok dlya otsenki genotoksicheskikh svoistv prirodnykh i sinteticheskikh soedinenii: Metodicheskie rekomendatsii]. Moscow; 2006. https://elibrary.ru/sevvqt (in Russian)

23. Durnev A.D., Merkulov V.A., Zhanataev A.K., Nikitina V.A., Voronina E.S., Seredenin S.B. Methodological recommendations for the assessment of DNA damage by alkaline gel electrophoresis of individual cells in pharmacological studies. In: Guidelines for Conducting Preclinical Studies of Medicines. Part 1 [Rukovodstvo po provedeniyu doklinicheskikh issledovanii lekarstvennykh sredstv. Chast’ 1]. Moscow: Grif i K; 2012: 115–28. https://elibrary.ru/wxwgpv (in Russian)

24. Larionov A.V., Volobaev V.P., Serdyukova E.S. The study of the parameters of DNA comets in healthy donors under different residential radiation parameters. Sovremennye problemy nauki i obrazovaniya. 2017; (6): 261. https://doi.org/10.17513/spno.27215 https://elibrary.ru/ynxzhy (in Russian)

25. Valueva S.V., Borovikova L.N., Sukhanova T.E., Lavrent’ev V.K., Volkov A.Ya. Influence of the nature of the stabilizing polymeric matrix on the self-organization of selenium nanoclusters. Butlerovskie soobshcheniya. 2011; 84(2): 266–71. https://doi.org/10.1134/S1070427211020170 https://elibrary.ru/ohqevh (in Russian)

26. Rodionova L.V., Shurygina I.A., Sukhov B.G., Popova L.G., Shurygin M.G., Artem’ev A.V., et al. Nanobiocomposite based on selenium and arabinogalactan: Synthesis, structure, and application. Zhurnal obshchei khimii. 2015; 85(2): 485–7. https://doi.org/10.1134/S1070363215020218 https://elibrary.ru/ufrbor (in Russian)

27. Qamar N., John P., Bhatti A. Toxicological and anti-rheumatic potential of Trachyspermum ammi derived biogenic selenium nanoparticles in arthritic Balb/c mice. Int. J. Nanomedicine. 2020; (15): 3497–509. https://doi.org/10.2147/IJN.S243718

28. Zhu C., Zhang S., Song C., Zhang Y., Ling Q., Hoffmann P. R., et al. Selenium nanoparticles decorated with Ulva lactuca polysaccharide potentially attenuate colitis by inhibiting NF-κB mediated hyper inflammation. J. Nanobiotechnology. 2017; 15(1): 20. https://doi.org/10.1186/s12951-017-0252-y

29. Korytov K.M., Dubrovina V.I., Pyatidesyatnikova A.B., Vityazeva S.A., Voitkova V.V., Prozorova G.F., et al. Assessment of toxic and immunoadjuvant properties of nanocomposites. Acta Biomedica Scientifica. 2019; 4(3): 102–9. https://doi.org/10.29413/ABS.2019-4.3.13 https://elibrary.ru/toskjp (in Russian)

30. Bano I., Skalickova S., Arbab S., Urbankova L., Horky P. Toxicological effects of nanoselenium in animals. J. Anim. Sci. Biotechnol. 2022; 13(1): 72. https://doi.org/10.1186/s40104-022-00722-2

31. Misra S., Boylan M., Selvam A., Spallholz J.E., Björnstedt M. Redox-active selenium compounds – from toxicity and cell death to cancer treatment. Nutrients. 2015; 7(5): 3536–56. https://doi.org/10.3390/nu7053536

32. Fernandes A.P., Gandin V. Selenium compounds as therapeutic agents in cancer. Biochim. Biophys. Acta. 2015; 1850(8): 1642–60. https://doi.org/10.1016/j.bbagen.2014.10.008

33. Lesnichaya M., Shendrik R., Titov E., Sukhov B. Synthesis and comparative assessment of antiradical activity, toxicity, and biodistribution of κ-carrageenan-capped selenium nanoparticles of different size: in vivo and in vitro study. IET Nanobiotechnol. 2020; 14(6): 519–26. https://doi.org/10.1049/iet-nbt.2020.0023

34. Loeschner K., Hadrup N., Hansen M., Pereira S.A., Gammelgaard B., Møller L.H., et al. Absorption distribution metabolism and excretion of selenium following oral administration of elemental selenium nanoparticles or selenite in rats. Metallomics. 2014; 6(2): 330–7. https://doi.org/10.1039/c3mt00309d

35. Zhang Z., Du Y., Liu T., Wong K.H., Chen T. Systematic acute and subchronic toxicity evaluation of polysaccharide-protein complex-functionalized selenium nanoparticles with anticancer potency. Biomater. Sci. 2019; 7(12): 5112–23. https://doi.org/10.1039/c9bm01104h

36. Ryabova Yu.V., Minigalieva I.A., Privalova L.I., Sutunkova M.P., Sakhautdinova R.R., Klinova S.V., et al. About combination of positive and negative outcomes of a subchronic exposure of rats to selenium oxide nanoparticles. Toksikologicheskii vestnik. 2022; 30(6): 386–94. https://doi.org/10.47470/0869-7922-2022-30-6-386-394 https://elibrary.ru/qeeqww (in Russian)

37. Tsyganovich O.A., Dybkova S.M., Siryk O.O., Golodyuk O.P., Prokopenko V.A., Zhovnir O.M. evaluation of cytotoxicity and genotoxicity of selenium nanoparticles stabilized with polyvinylpyrrolidone. Veterinary biotechnology. 2021; 38(38): 166–73. https://doi.org/10.31073/vet_biotech38-14 https://elibrary.ru/hcpthh

38. Indumathy M., Raj S.S., Arumugham I.M., Kumar R.P. Assessment of toxicity of selenium nanoparticle varnish using HepG2 cell lines: in vitro study. J. Pharm. Res. Int. 2020; 32(27): 33–9. https://doi.org/10.9734/JPRI/2020/v32i2730853

39. Hozyen H.F., El Shamy A.A. Screening of genotoxicity and oxidative stress effect of selenium nanoparticles on ram spermatozoa. Cur. Sci. Int. 2018; 7(4): 799–807.

40. Khalil W.A., El-Harairy M.A., Zeidan A.E.B., Hassan M.A.E. Impact of selenium nanoparticles in semen extender on bull sperm quality after cryopreservation. Theriogenology. 2018; (126): 121–7. https://doi.org/10.1016/j.theriogenology.2018.12.017

41. He Y., Chen S., Liu Z., Cheng C., Li H., Wang M. Toxicity of selenium nanoparticles in male Sprague-Dawley rats at supranutritional and nonlethal levels. Life Sciences. 2014; 115(1–2): 44–51. https://doi.org/10.1016/j.lfs.2014.08.023

42. Hadrup N. Loeschner K., Skov K., Ravn-Haren G., Larsen E.H., Mortensen A., et al. Effects of 14-day oral low dose selenium nanoparticles and selenite in rat-as determined by metabolite pattern determination. Peer J. 2016; (4): e2601. https://doi.org/10.7717/peerj.2601