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Experimental study on the influence of iron oxide nanoparticles on rats after a single intratracheal administration

Experimental study on the influence of iron oxide nanoparticles on rats after a single intratracheal administration

ISSN 2223-6775 Ukrainian journal of occupational health Vol.16, No 4, 2020

Experimental study on the influence of iron oxide nanoparticles on rats after a single intratracheal administration

Trakhtenberg І. М., Dmytrukha N. М., Korolenko T. K., Lehkostup L. A., Lahutina O. S., Kozlov K. P., Bakalo L. V.

https://doi.org/10.33573/ujoh2020.04.251

State Institution “Kundiiev Institute of Occupational Health of the National Academy of Medical Sciences of Ukraine”, Kyiv, Ukraine

Full article (PDF), UKR

Introduction. Iron oxides (Fe2O3, Fe3O4) in the form of nanoparticles (NPs) is a promising material for industry, medicine and pharmacy. The iron oxide NPs can enter the human body with air, food and medicines. The availability of special physicochemical properties in NPs (small size, large surface area, increased reactivity and biological action) requires thorough research to assess their safety. Study the behaviour of iron oxides nanoparticles on entering the body, namely, their transport, distribution, and influence on the functioning of organs and systems, remains an important issue.

The aim of this research is experimental studies on the effect of Fe2O3 colloidal solutions of different dispersion on rats after a single intratracheal administration.

Materials and methods. The study was carried out on 24 Wistar male rats weighing 220-260 g, divided into two experimental groups. Rats were intratracheally injected once with colloidal solutions of Fe2O3 19 nm and 400 nm particles at a dose of 10 mg/kg for iron, the control group was injected with 0.9% saline in the same way. On the 21st day of the experiment, the rats were sacrificed, and body and organ weighted, haematological parameters (complete blood count with counting leukocyte subpopulations, coagulogram), biochemical parameters characterizing the state of the liver, kidneys, protein and lipid metabolism, and nonspecific natural immunity were determined.

Results and discussion. It was found that a single intratracheal administration of colloidal solutions of Fe2O3 to rats did not affect the body and organ weight. 19 nm Fe2O3 led to a slight increase in the iron content in the lungs, thymus and kidneys, while 400 nm Fe2O3 caused a significant increase in iron concentration in the lungs, liver, spleen, thymus, and kidneys as compared to the control group. Changes in hematological parameters were characterized by a decrease in the level of hemoglobin and the number of erythrocytes, the absolute number of lymphocytes and granulocytes, an increase in the level of zinc protoporphyrin and the percentage of monocytes. The data indicate the development of anemia and activation of nonspecific immunity cells. The increase in the number of platelets, fibrinogen and prothrombin index, and decrease in thrombin time indicate the influence of Fe2O3 nanoparticles on the blood coagulation process. Elevated levels of C-reactive protein and circulating immune complexes in the serum can be signs of formation of an inflammatory process in the body.

Conclusions. The accumulation of iron in the heart, liver, spleen, kidneys after a single intratracheal injection of 400 nm Fe2O3 indicates their increased accumulation capacity. Disturbances in the cellular and protein composition of the blood indicate a potential hematotoxic, pro-inflammatory, and atherogenic effect, especially for Fe2O3 NPs of 19 nm.

Keywords: colloidal solutions of iron oxide Fe2O3, intratracheal administration, toxicity, safety.

References

  1. Narysy z toksykolohii vazshky metaliv. Vypusk V- Zalizo [Essays on the toxicology of heavy metals. Issue V-Iron], (2017), (ed. I.M. Trakhtenberg). Аvicennа, Kyiv, Ukraine. ISBN 978-966-2144-96-3.
  2. Albretsen Jay. (2006), “The toxicity of iron, an essential element”,. Veterinary Medicine, 2, 82–90.
  3. Lubyanova I.P. (2013), Izbytochnoye zhelezo i patologiya u robochikh svarochnykh professiy [Excessive iron and pathology in workers of welding professions], Avicenna, Kyiv, Ukraine. ISBN 978-966-2144-59-8.
  4. Patel R.R, Yi E.S., Ryu J.H. (2009), “Systemic iron overload associated with welder's siderosis”, The American Journal of the Medical Sciences. 337(1), 57–59. https://doi.org/10.1097/01.MAJ.0000308933.80112.49
  5. Ghio A.J. (2009), “Disruption of iron homeostasis and lung disease”, Biochim Biophys Acta. 1790 (7), 731–739. https://doi.org/10.1016/j.bbagen.2008.11.004
  6. Dudchenko N. О. (2009), “Magnetic nanoparticles for medical and biological purposes: methods of synthesis, study of properties, application”, Nanosystems, nanomaterials, nanotechnologies, 7(4), 1027-1059.
  7. Сhekhun V.F. (2011), “Sozdanie novyh lekarstvennyh form na osnove nanocompozitnyh materialov dlay reshenia sovremennyh problem onkologii. Nanosystemy, nanomaterialy, nanotehnologii». Zb.nauk.prac. – Kyiv:1, 261-274. Ukraine
  8. Trakhtenberg I. M., Dmytrukha N. M. (2013), “Nanoparticles of metals, methods of definition, spheres of use, physicochemical and toxic properties”, Ukrainian Journal of Occupational Health, 4 (37), 62–74. https://doi.org/10.33573/ujoh2013.04.062
  9. Liu S.Y., et al. (2008), “Toxicology studies of a superparamagnetic iron oxide nanoparticle in vivo”, Mater. Res., 47-50,1097–1100. https://doi.org/10.4028/www.scientific.net/AMR.47-50.1097
  10. Katsnelson B. A., Privalova L. I., Kuzmin S. V. et al. (2010), “Experimental data on the assessment of pulmonotoxicity and resorptive toxicity of magnetite particles (Fe3O4) of the nano- and micrometer range”, Toksikologicheskiy vestnik, 2, 17–24.
  11. Zhu M.T., Feng W.Y., Wang B. [et al.].(2008),“Comparative study of pulmonary responses to nano- and submicron-sized ferric oxide in rats”, Toxicology, 247(2–3), 102–111. https://doi.org/10.1016/j.tox.2008.02.011
  12. Lugovskyi S. P., Dmytrukha N.M., Didenko M.N., Bakalo L.V., Lahutina O.S, Melnik N.A. (2019), “Morpho-functional changes in internal organs of rats in long-term administration of iron oxide nanoparticles into abnomical cavity”, Ukrainian Journal of Occupational Health, 15 (3), 228-239. https://doi.org/10.33573/ujoh2019.03.228
  13. 13. European convention for the protection of vertebrate animal used for experimental and other scientific purposes. (1986), Counsul of Europe, Strasburg.
  14. 14. Berkalo L. V., Bobovich O. V., Bobrova N. O. (2003), “Metody klinichnykh ta eksperymentalnykh doslidzhen v medytsyni” [Methods of clinical and experimental research in medicine], (ed. Kaideshev I.P.), Polimet, Poltava, Ukraine.
  15. 15. Antamonov M.U. (2017), Matematicheskaia obrabotka i analiz mediko-biologicheskih dannyh [Mathematical processing and analysis of medical and biological data]. 2-еd., Кiev, Ukraine.
  16. Profilaktychna toksykologia ta medychna ekologia.Vybrani lekcii dlya naukovtsiv, likariv ta studentiv [Preventive toxicology and medical ecology. Selected lectures for scientists, doctors and students], 2012, (ed. I. Trakhtenberg), Аvicennа, Kyiv, Ukraine. ISBN 978-966-2144-27-7.
  17. 17. Myslytsky V.F., Podolian S.K. (1999), “Pathological changes of platelet-vascular and coagulation hemostasis under the influence of lead chloride and their correction using a synthetic analogue of prostacyclin”, Physiological Journal, 4, 99-104.
  18. Kirichenko М.N., Bulychov N.А., Chaikov L.L., Каzаrian М.А., Маsаlоv М.А. (2017), “Influence of iron oxide nanoparticles (lll) on blood clotting according to light scattering data”, XIII International Conference on pulsed lasers and laser applications A M P L, September 10-15, Tomsk, Russia. https://doi.org/10.1117/12.2303510
  19. Zhu, M.T., Wang, B., Wang, Y., Yuan, L. et al. (2011), “Endothelial dysfunction and inflamation induced by iron oxide nanoparticle exposur: Risk factors for early atherosclerosis”, Toxicol. Letter, 203 (2), 162-171. https://doi.org/10.1016/j.toxlet.2011.03.021