Biological effect of the Fe₃O₄AG nanocomposite upon subacute exposure to the body in white rats

Introduction. Currently, magnetic nanoparticles of iron oxides are widely used in many branches of human activity. Among the production technologies, the most dangerous are metallurgical production, electric arc and gas welding, metal smelting and cutting at steel mills, during which metal oxide nanoparticles are formed in significant quantities.

Materials and methods. Male white rats were orally introduced for 10 days with an aqueous solution of Fe₃O₄AG (iron oxide nanoparticles stabilized with the polymer arabinogalactan) at doses of 500 µg/kg. After the end of the exposure, the animals were decapitated under light ether anesthesia. Blood, brain, liver, and kidneys were taken for biochemical, histological, and genotoxic analysis using the DNA comet method.

Results. Studies have shown a decrease in the amount of hemoglobin per unit of blood, a decrease in the total number of neurons in brain tissue, an increase in the area of the renal glomeruli chamber and an increase in DNA damage in nucleated blood cells.

Limitations. The experiment is limited to the study of biochemical parameters of peripheral blood, histological analysis of brain, liver and kidney tissue, as well as the study of the effect of iron oxide nanocomposite at doses of 500 µg/kg on male white rats the next day after a ten-day exposure.

Conclusion. The biological effect of iron oxide nanocomposite is characterized by a decrease in the amount of hemoglobin, DNA fragmentation in nucleated blood cells, an expansion of the chamber area of the renal glomeruli of the renal cortex, and a decrease in the total number of neurons in the sensorimotor cortex.

Compliance with ethical standards. The study was approved by the local Ethics Committee of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation (Protocol No. 1 dated December 18, 2017), conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), Directive of the European Parliament and of the Council of the European Union 2010/63/EC dated September 22, 2010 on the protection of animals used for for scientific purposes.

Contribution:
Titov E.A. – concept and design of the study, conducting histological examinations, data collection and processing, statistical data processing, writing, editing;
Neighbor L.M. – concept and design of the study, editing;
Novikov M.A. – concept and design of the study, conducting intragastric drug administration;
Pankova A.A. – conducting intragastric administration and histological examination;
Abramova V.A. – conducting a study of the genotoxicity of the drug;
Vokina V.A. – conducting biochemical studies;
Lisetskaya L.G. – assessment of the drug content in organs;
Alexandrova G.P. – synthesis and investigation of the physico-chemical properties of the nanocomposite.
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.

Funding. The work was carried out according to the research plan within the framework of the state assignment.

Received: February 17, 2025 / Revised: April 7, 2025 / Accepted: June 26, 2025 / Published: July 31, 2025

1. Cornell R.M., Schwertmann U. The Iron Oxides. Weinheim: Wiley-VCH; 2003.

2. 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

3. 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

4. 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. https://doi.org/10.1166/jbn.2019.2689

5. 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

6. Zanganeh S., Ho J.Q., Aieneravaie M. Chapter 9 – Drug Delivery. In: Iron Oxide Nanoparticles for Biomedical Applications. Elsevier; 2018: 247–71. https://doi.org/10.1016/B978-0-08-101925-2.00008-5

7. Zaytseva M.P., Muradova A.G., Sharapaev A.I., Yurtov E.V., Grebennikov I.S., Savchenko A.G. Fe304/Si02 core shell nanostructures: preparation and characterization. Russ. J. Inorg. Chem. 2018; 63: 1684–8. https://doi.org/10.1134/s0036023618120239

8. Miao C., Yang L., Wang Z., Luoa W., Li H., Luo P., et al. Lipase immobilization on amino-silane modified superparamagnetic Fe3O4 nanoparticles as biocatalyst for biodiesel production. Fuel. 2018; 224: 774–82. https://doi.org/10.1016/j.fuel.2018.02.149

9. Tsurin V.A., Yermakov A.Y., Uimin M.A., Mysik A.A., Shchegoleva N.N., Gaviko V.S., et al. Synthesis, structure, and magnetic properties of iron and nickel nanoparticles encapsulated into carbon. Physics of the Solid State. 2014; 56(2): 287–300. https://doi.org/10.1134/S1063783414020309 https://elibrary.ru/skmkvx

10. Chen Z., Geng Z., Tao T., Wang Z. Shape-controlled synthesis of Fe3O4 rhombic dodecahedrons and nanodiscs. Mater. Lett. 2014; 117: 10–3. https://doi.org/10.1016/j.matlet.2013.11.076

11. Leonenko N.S., Demetska O.V., Leonenko O.B. Changes in concentrations of nanoparticles in working air under production environment over time. Ukrainian Journal Of Modern Problems Of Toxicology. 2019; (1): 53–61. https://elibrary.ru/essgfw

12. Sutunkova M.P. Experimental data and methodological considersations for justification of iron oxide nanoparticles maximum allowable concentration in occupsational air. Toksikologicheskii vestnik. 2016; (6): 11–7. (in Russian)

13. Zaitseva N.V., Ulanova T.S., Zlobina A.V., Volkova M.V., Gileva M.I. Investigations into nanoscale particles as part of industrial aerosols and particulate matter in the air of working area. Toksikologicheskii vestnik. 2017; (1): 20–6. https://doi.org/10.36946/0869-7922-2017-1-20-26 https://elibrary.ru/yfqfkt (in Russian)

14. 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): 41–4. https://elibrary.ru/vxpoin (in Russian)

15. Korzhevskii D.E. Summary of the Basics of Histological Technique for Doctors and Laboratory Technicians [Kratkoe izlozhenie osnov gistologicheskoi tekhniki dlya vrachei i laborantov-gistologov]. St. Petersburg: Krof; 2005. https://elibrary.ru/rwxfhf (in Russian)

16. Polozyuk O.N., Ushakova T.M. Hematology: a Textbook [Gematologiya: uchebnoe posobie]. Persianovskii; 2019. (in Russian)

17. Durnev A.D., Zhanataev A.K., Anisina E.A., Sidneva E.S., Nikitina V.A., Oganesyants L.A., et al. Methodological recommendations. The use of alkaline gel electrophoresis of isolated cells to evaluate the genotoxic properties of natural and synthetic compounds. Moscow; 2006. https://elibrary.ru/sevvqt (in Russian)

18. Medvedeva S.A., Aleksandrova G.P., Grishchenko L.A., Tyukavkina N.A., Chetverikova T.D., Krasnikova I.M., et al. A drug with antianemic and immunomodulatory activity. Patent RF № 2208440 C2; 2003. (in Russian)

19. Nikolaev A.A., Belopasov V.V. Ferroptosis in the pathogenesis of brain tumors. Klinicheskaya praktika. 2022; 13(4): 68–73. https://doi.org/10.17816/clinpract114787 https://elibrary.ru/qqxmsp (in Russian)

20. Aleksandrova G.P., Krasnikova I.M., Grishchenko L.A., Medvedeva S.A., Chetverikova T.D. Synthesis and antianemic activity of a nanoscale ferroarabinogalactane biocomposite. Khimiya rastitel‘nogo syr‘ya. 2010; (3): 37–42. https://elibrary.ru/mxsevl (in Russian)

21. Doak S.H., Dusinska M. NanoGenotoxicology: present and the future. Mutagenesis. 2017; 32(1): 1–4. https://doi.org/10.1093/mutage/gew066

22. Tyutrina V.A., Sosedova L.M., Novikov M.A. Analysis of the genotoxicity of iron nanocomposite arabinogalactan using the DNA comet method. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2024; 103(10): 1251–6. https://doi.org/10.47470/0016-9900-2024-103-10-1251-1256 https://elibrary.ru/ngqwic (in Russian)