Analysis of toxicity of iron oxide nanocomposite encapsulated in a polymer matrix of arabinogalactan

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Abstract

Introduction. The article presents a toxicity analysis of the Fe3O4 nanocomposite encapsulated in the natural polymer matrix of arabinogalactan (AG). A study was devoted to forming and developing the biological response of organisms to subacute administration of this nanocomposite.

Materials and methods. White outbred male rats weighing 200-220 gr. were used in this study. For ten days, a test drug solution was administered orally to animals with a probe at a dose of 500 μg of iron per kilogram of body weight. Then, using histological and immunohistochemical analysis methods, the severity of the biological response of the organism to the introduction of this nanocomposite was evaluated. An analysis was made of the state of tissue of the liver, kidneys, and sensorimotor cortex. The number of neurons with the proapoptotic caspase three protein expression, anti-apoptotic bcl-2 protein, and HSP 70 stress protein was determined in the sensorimotor cortex tissue.

Results. With intragastric administration to experimental animals, there was a violation of normal blood rheology in liver and kidney tissue, protein dystrophy of hepatocytes, expansion of perivascular spaces of brain tissue, and a decrease in the total number of sensorimotor cortex neurons per unit area. Immunohistochemical analysis of tissue of the sensorimotor cortex for expression of pro-and anti-apoptotic proteins and the expression of HSP 70 protein showed a sharp increase in the number of neurons with the expression of HSP 70 stress protein.

Discussion. The nature of the detected changes indicates the occurrence of compensatory-adaptive reactions in the organism in response to the effect of FeAG. The lack of expression of caspase 3 protein eliminates the development of apoptosis.

About the authors

Eugeny A. Titov

East-Siberian Institute of Medical and Ecological Research

Author for correspondence.
Email: g57097@yandex.ru
ORCID iD: 0000-0002-0665-8060

MD, Ph.D. senior researcher of the Laboratory of biomodeling and translational medicine) of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation.

e-mail: g57097@yandex.ru

Russian Federation

Larisa M. Sosedova

East-Siberian Institute of Medical and Ecological Research

Email: noemail@neicon.ru
ORCID iD: 0000-0003-1052-4601
Russian Federation

Mkhail A. Novikov

East-Siberian Institute of Medical and Ecological Research

Email: noemail@neicon.ru
ORCID iD: 0000-0002-6100-6292
Russian Federation

References

  1. Shilov I.P., Ivanov A.V., Alekseev Yu.V., Rumyantseva V.D., Ryabov A.S., Shchelkunova A.E., et al. New approaches in theranostics of neoplasms based on ytterbium porphyrin complexes. In: Lasers in Science, Technology, Medicine. Collection of Scientific Papers of the XXIX International Conference [Lazery v nauke, tekhnike, meditsine. Sbornik nauchnykh trudov XXIX Mezhdunarodnoy konferentsii]. Vladivostok; 2018: 187–90. (in Russian)
  2. Powers K.W., Palazuelos M., Moudgil B.M., Roberts S.M. Characterization of the size, shape, and state of dispersion of nanoparticles for toxicological studies. Nanotoxicology. 2007; 1(1): 42–51.
  3. Polunina O.A. Prospects for the use of metal-containing composites. In: Integration of Science and Practice in Modern Conditions: Materials of the VI International Scientific Practical Conference [Integratsiya nauki i praktiki v sovremennykh usloviyakh: Materialy VI Mezhdunarodnoy nauchno-prakticheskoy konferentsii]. Taganrog; 2016: 79–84. (in Russian)
  4. Pal’tsev M.A., Kiselev V.I., Sveshnikov P.G. Nanotechnology in medicine. Vestnik Rossiyskoy akademii nauk. 2009; 79(7): 627–36. (in Russian)
  5. Lozovskaya E.A., Silkin I.I., Sukhov B.G. The influence of the nano-preparation “Selenium” on the functional condition of cells of the Ehrlich ascitecarcinoma (in vivo). Vestnik Krasnoyarskogo gosudarstvennogo agrarnogo universiteta. 2015; (9): 56–9. (in Russian)
  6. Medvedeva E.N., Babkin V.A., Ostroukhova L.A. Larch arabinogalactan – properties and prospects of use. Khimiya rastitel’nogo syr’ya. 2003; (1): 27–37. (in Russian)
  7. Song C., Sun W., Xiao Y., Shi X. Ultrasmall iron oxide nanoparticles: synthesis, surface modification, assembly, and biomedical applications. Drug Discov. Today. 2019; 24(3): 835–44. https://doi.org/10.1016/j.drudis.2019.01.001
  8. Dadfar S.M., Roemhild K., Drude N.I., von Stillfried S., Knüchel R., Kiessling F., et al. Iron oxide nanoparticles: Diagnostic, therapeutic and theranostic applications. Adv. Drug Deliv. Rev. 2019; 138: 302–25. https://doi.org/10.1016/j.addr.2019.01.005
  9. Wu C.Y., Chen Y.C. Riboflavin immobilized Fe3O4 magnetic nanoparticles carried with n-butylidenephthalide as targeting-based anticancer agents. Artif. Cells Nanomed. Biotechnol. 2019; 47(1): 210–20. https://doi.org/10.1080/21691401.2018.1548473
  10. Lugert S., Unterweger H., Mühlberger M., Janko C., Draack S., Ludwig F., et al. Cellular effects of paclitaxel-loaded iron oxide nanoparticles on breast cancer using different 2D and 3D cell culture models. Int. J. Nanomedicine. 2018; 14: 161–80. https://doi.org/10.2147/ijn.s187886
  11. Zhang L., Jin R., Sun R., Du L., Liu L., Zhang K., et al. Superparamagnetic iron oxide nanoparticles as magnetic resonance imaging contrast agents and induced autophagy response in endothelial progenitor cells. J. Biomed. Nanotechnol. 2019; 15(2): 396–404.
  12. Xie L., Jin W., Chen H, Zhang Q. Superparamagnetic iron oxide nanoparticles for cancer diagnosis and therapy. J. Biomed. Nanotechnol. 2019; 15(2): 215–416. https://doi.org/10.1166/jbn.2019.2678
  13. Amirkhanov R.N., Zarytova V.F., Zenkova M.A. Inorganic nanoparticles as nucleic acid transporters into eukaryotic cells. Uspekhi khimii. 2017; 86(2): 113–27. (in Russian)
  14. Shimanovskiy N.L. Directed drug transport using iron oxide nanoparticles. Rossiyskiy khimicheskiy zhurnal. 2012; 56(3-4): 126–45. (in Russian)
  15. Kovaleva N.Yu., Raevskaya E.G., Roshchin A.V. Aspects of nanomaterial safety: nanosafety, nanotoxicology, nanoinformatics. Khimicheskaya bezopasnost’. 2017; 1(2): 44–87. https://doi.org/10.25514/CHS.2017.2.10982 (in Russian)
  16. Sahoo S.K., Parveen S., Panda J.J. The present and future of nanotechnology in human health care. Nanomedicine. 2003; 3(1): 20–31. https://doi.org/10.1016/j.nano.2006.11.008
  17. Trofimov B.A., Sukhov B.G., Aleksandrova G.P., Medvedeva S.A., Grishchenko L.A., Mal’kina A.G., et al. Nanocomposites with magnetic,optical, catalytic, and biologically active properties based on arabinogalactan. Doklady Chemistry. 2003; 393(4–6): 287–93. https://doi.org/10.1023/B:DOCH.0000010332.05066.4b
  18. Koo J.S., Lee S.Y., Azad M.O.K., Kim M., Hwang S.J., Nam S.Yi., et al. Development of iron (II) sulfate nanoparticles produced by hot-melt extrusion and their therapeutic potentials for colon cancer. Int. J. Pharm. 2019; 558: 388–95. https://doi.org/10.1016/j.ijpharm.2019.01.018
  19. Anbouhi T.S., Esfidvajani E.M., Nemati F., Haghighat S., Sari S., Attar F., et al. Albumin binding, anticancer and antibacterial properties of synthesized zero valent iron nanoparticles. Int. J. Nanomedicine. 2018; 14: 243–56. https://doi.org/10.2147/ijn.s188497
  20. Yen H.J., Hsu S.H., Tsai C.L. Cytotoxicity and immunological response of gold and silver nanoparticles of different sizes. Small. 2009; 5(13): 1553–61. https://doi.org/10.1002/smll.200900126
  21. Potapov A.I., Rakitskiy V.N., Tulakin A.V., Lutsenko L.A., Il’nitskaya A.V., Egorova A.M., et al. Safety of nanoparticles and nanomaterials for environmental and occupational space. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2013; 92(3): 8–14. (in Russian)
  22. Sosedova L.M., Novikov M.A., Titov E.A., Rukavishnikov V.S. Evaluation of biologic effects caused by nano-silver influence on brain tissue of experimental animals. Meditsina truda i promyshlennaya ekologiya. 2015; (4): 26–30. (in Russian)
  23. Titov E.A., Sosedova L.M., Novikov M.A. Alteration of white rats brain tissue inducted by assessment of silver nanocomposite incapsulated in polymer matrix. Patologicheskaya fiziologiya i eksperimental’naya terapiya. 2015; 59(4): 41–5. (in Russian)
  24. Korzhevskiy D.E. Summary of the Basics of Histological Technique for Physicians and Laboratory Technologists-Histologists [Kratkoe izlozhenie osnov gistologicheskoy tekhniki dlya vrachey i laborantov-gistologov]. St. Petersburg: Krof; 2005. (in Russian)
  25. Dyatlova A.S., Dudkov A.V., Lin’kova N.S., Khavinson V.Kh. Molecular markers of caspase-dependent and mitochondrial apoptosis: the role of pathology and cell senescence. Uspekhi sovremennoy biologii. 2018; (2): 126–37. https://doi.org/10.7868/S0042132418020023 (in Russian)
  26. Svanidze I.K., Museridze D.P., Didimova E.V., Gvinadze N.N., Gegenava L.G., Bregvadze I.A. Correction of changes induced by toluene in the cortical and subcortical structures of albino rat brain. Izvestiya Rossiyskoy akademii nauk. Seriya biologicheskaya. 2007; (3): 325–8. (in Russian)
  27. Kumar G.S., Kulkami A., Khurana A., Kaur J., Tikoo K. Selenium nanoparticles involve HSP-70 and SIRT1 in preventing the progression of type 1 diabetic nephropathy. Chem. Biol. Interact. 2014; 223: 125–33.
  28. Ahamed M., Posqai R., Gorey T.J., Nielsen M., Hussain S.M., Rowe J.J. Silver nanoparticles induced heat shock protein 70, oxidative stress and apoptosis in Drosophila melanogaster. Toxicol. Appl. Pharmacol. 2010; 242(3): 263–9. https://doi.org/10.1016/j.taap.2009.10.016
  29. Andreeva L.I. Theoretical and applied value of heat shock proteins 70 kDa; possibility of practical application and pharmacological correction. Obzory po klinicheskoy farmakologii i lekarstvennoy terapii. 2002; 1(2): 2–14. (in Russian)
  30. Shchelochenkov S.V., Petrova M.B., Dzhulay G.S., Kileynikov D.V. Morphological changes in rat liver, reproducing nonalcoholic fatty liver disease in experimental postoperative hypothyrosis. Verkhnevolzhskiy meditsinskiy zhurnal. 2017; 16(1): 14–9. (in Russian)

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