You are using an outdated browser. For a faster, safer browsing experience, upgrade for free today.

Distribution dynamics of iron and other elements in blood and organs of rats following administration of iron oxide nanoparticles of varied sizes

ISSN 2223-6775 Ukrainian journal of occupational health Vol.19, No 4, 2023

Distribution dynamics of iron and other elements in blood and organs of rats following administration of iron oxide nanoparticles of varied sizes

Dmytrukha N.M., Andrusyshyna I.M., Legkostup L.A., Kozlov K.P., Gerasimova O.V.
State Institution «Kundiiev Institute of Occupational Health of the National Academy of Medical Sciences of Ukraine», Kyiv

Full article (PDF): ENG / UKR

Introduction: The widespread application of iron oxide nanoparticles (Fe2O3 NPs) in diverse industrial sectors, notably in medicine for purposes like MRI contrast enhancement, hyperthermia-induced tumor destruction, and targeted drug delivery, necessitates a comprehensive understanding of their accumulation dynamics and interactions with biological structures within the human body. The dearth of data on the distribution of these NPs in the body and their mechanisms of interaction poses a significant challenge. Excessive iron levels in the body can trigger oxidative stress and metabolic disorders, contributing to the development of various pathological conditions such as atherosclerosis, cardiovascular diseases, and degenerative changes in the nervous and pulmonary systems.

Objective: This study aims to elucidate the accumulation and distribution patterns of iron (Fe) in blood and internal organs subsequent to prolonged administration of colloidal solutions containing Fe2O3 NPs of sizes 19 nm and 75 nm to rats. Additionally, the study investigates the impact on the balance of essential elements, including calcium (Ca), zinc (Zn), copper (Cu), and magnesium (Mg).

Materials and Methods: Experimental evaluations of Fe and other element accumulations (Ca, Fe, Zn, Mg) were conducted in the blood and internal organs of rats following the introduction of colloidal solutions of iron oxide nanoparticles with sizes of 19 nm and 75 nm. Metal content was determined using optical emission spectroscopy with inductively coupled plasma on a Perkin Elmer Optima 2100 DV device. Measurements were taken after 30 injections of Fe2O3 solutions and again after a 30-day post-exposure period.

Results: The study revealed a substantial increase in free iron content in the whole blood and internal organs of rats after 30 injections of colloidal solutions of Fe2O3 with NPs of both sizes. Even 30 days after cessation of NP administration, iron levels continued to rise in the blood and organs. Prolonged intake of Fe2O3 colloidal solutions induced an imbalance of essential metals (Ca, Zn, Cu, Mg) in the blood and organs, with more pronounced discrepancies observed with the introduction of 19 nm Fe2O3 NPs. The acquired data unequivocally reveal a notable escalation in the concentration of iron within the bloodstream of the experimental rats, coupled with its entry and accumulation in various organs, suggesting a protracted removal period from the body. Notably, prolonged ingestion of Fe2O3 colloidal solutions in rat models was found to disrupt the equilibrium of essential metals (Ca, Zn, Cu, Mg) within both blood and organs, resulting in manifestations of either deficiency or excess. Notably, a more pronounced perturbation in elemental balance was discerned with the introduction of 19 nm Fe2O3 nanoparticles (NPs). This observed iron accumulation raises concerns about its potential to incite oxidative stress, thereby contributing to the onset of conditions such as liver cirrhosis and type 2 diabetes. Furthermore, the identified imbalance in elements Ca, Zn, Cu, Mg may foster the development of trace element-related disorders, leading to functional impairments in metal-containing proteins, enzymes, and metabolic processes.

Conclusions: The identified differences in iron accumulation and the observed imbalance of essential elements suggest a potential negative impact on the functioning of organs, metal-containing proteins, and enzymes. These findings underscore the importance of cautious use of iron oxide nanoparticles in medical applications, necessitating preventive measures and interventions to address potential microelement diseases associated with their prolonged intake.

Keywords: iron oxide, nanoparticles, toxicity, elemental imbalance, macro- and microelements.


  1. Chekman IS. [Nanoparticles: properties and application prospects]. Ukr biokhimichnyi zhurnal. 2009;81(1):122- Ukrainian.
  2. Dudchenko NO. [Magnetic nanoparticles for medical and biological purposes: synthesis methods, properties research, application]. Nanosystemy, nanomaterialy, nanotekhnolohii. 2009;7(4):1027-
  3. Buzea C, Pachego I, Robble K. Nanomaterial and nanoparticles: Sources and toxicity. Biointerphases. 2009;2(4):49-55. DOI:
  4. Nel A, Xia T, Madler L, et al. Toxic potential of materials at the nanolevel. Science. 2006;311(5761):622-7. DOI:
  5. Trakhtenberg IM, Dmytrukha NM. [Nanoparticles of metals, methods of definition, spheres of use, physico-chemical and toxic powers]. Ukrainian Journal of Occupational Health. 2013;4(37):62-74. DOI: Ukrainian.
  6. Leonenko N, Demetska OV, Leonenko OB. [Specifics of physicochemical properties and toxic action of nanomaterials - to the problem of assessing their impact on living organisms (literature review)]. Suchasni problemy toksykolohii, kharchovoi ta khimichnoi bezpeky. 2016;1:64-76. Ukrainian.
  7. Kartel MT, Tereshchenko VP. [The concept of the methodology of identification and toxicological studies of nanomaterials and risk assessment for the human body and the environment during their production and application.] In: Khymyia, fyzyka y tekhnolohyia poverkhnosty : Mezhved. sbornyk nauchn. trudov Vol Kyiv: Naukova dumka; 2008. P.565-83. Ukrainian.
  8. Singh A, Patel T, Hertel J, et al. Safety of ferumoxytol in patients with anemia and CKD. J. Kidney Dis. 2008;52(5):907-15. DOI:
  9. Zhu MT, Feng WY, Wanga B, et al. Comparative study of pulmonary responses to nano- and submicron-sized ferric oxide in rats. 2008;247(2-3):102-11. DOI:
  10. Weissleder R, Stark DD, Engelstad BL, et al. Super paramagnetic iron oxide: pharmacokinetics and toxicity. AJR Am. J. 1998;152(1):167-73. DOI:
  11. Trachtenberg IM, academician of the National Academy of Sciences of Ukraine, editor [Essays on the toxicology of heavy metals. Volume 5 – Iron]. Kyiv: Avitsena; 2017. Ukrainian. ISBN 978-966-2144-96-3.
  12. Huang X. Iron overload and its association with cancer risk in humans: evidence for iron as carcinogenic metal. Mutal research. 2003;533(1-2):153-71. DOI:
  13. Lubianova YP. [Excess iron and pathology in welding workers]: academician Kundiev YuI, editor. Kyiv: Avitsena; 2017. Russian.
  14. European convention for the protection of vertebrate animal used for experimental and other scientific purposes. Strasburg: Council of Europe;1986.
  15. Andrusyshyna IM, Lampeka OH, Holub I, Lubianova IP, Kharchenko TD [Assessment of mineral metabolism disorders in professional contingents using the method of atomic emission spectrometry with inductively coupled plasma] : methodological recommendations (111)72.14/133.14. Kyiv: Avitsena; Ukrainian.
  16. Oberlys D. The biological role of macro- and microelements in humans and animals. : Nauka; 2008. Russian
  17. Iavicoli I, Fontana L, Leso V, Bergamaschi A. The Effects of Nanomaterials as Endocrine Int. J. Mol. Sci. 2013;14:16732-801. DOI:
  18. Mokliak YeV, Vazhnycha OM, Andrusyshyna IM. [The effect of composite nanoparticles of magnetite on the content of iron in the organs and blood plasma of rats under conditions of acute blood loss]. Farmakolohiia ta likarska toksykolohiia. 2014;6(41):51-8. Ukrainian.
  19. Kumah EA, Fopa RD, Harati S, et al. Human and environmental impacts of nanoparticles: a scoping review of the current literature. BMC public health. 2023;23:1059. DOI:
  20. Lozovska YuV, Andrusyshyna IM, Lukianova NYu, Burlaka AP, Naleskina LA, Todor IN, Chekhun VF. The influence of lactoferrin on elemental homeostasis and actinity of metal-containing enzymes in rats with walker-256 carcinosarcoma. Experimental oncology. 2019;1(41):20-5. DOI:
  21. Rodrigues GP, Cozzolino SM, Nascimento MD, et al. Mineral status and superoxide dismutase enzyme activity in Alzheimer’s disease. J Trace Elem Med Biol. 2017;44:83-7. DOI: