Evaluation of the neurotropism of iron (II, III) oxide nanocomposite in the course of the post-exposure period, based on changes in electroencephalography parameters and behavioral reactions in rats

Introduction. Iron oxide nanoparticles (NPs) are widely used in medicine. However, the mechanisms of their toxicity are not fully understood. In particular, due to their ability to accumulate in the nervous system (NS), it is necessary to investigate their remote neurotoxic effects.

The aim of the study was to evaluate the neurotoxicity of an iron oxide nanocomposite (NC) encapsulated in an arabinogalactan (AG) matrix over the post-exposure period, based on changes in electroencephalography (EEG) parameters and behavioral responses in male rats.

Materials and methods. The experiment was performed on mongrel, sexually mature male albino rats (n = 60). The experimental groups received NC intragastric administration for 10 days at doses of 500 µg/kg (Fe₃O₄AG 500) and 5000 µg/kg (Fe₃O₄AG 5000) body weight. The control groups received 0.5 ml of 0.9% NaCl. Rats’ behavior was studied using the «open-field» method using the EthoStudio setup. EEG recording and analysis were performed using a «Neuron-Spectr-1/V» device. Rats were examined immediately and 6 months after the end of exposure.

Results. In the early post-exposure period, the distance traveled increased in the Fe₃O₄AG 5000 group compared to intact animals. In the 1^st period, the average power of alpha and beta-1 rhythms increased in the Fe₃O₄AG 500 group in lead Fp1-A1 compared to the control group. In rats, immediately after receiving NC in doses of 500 µg/kg and 5000 µg/kg, an increase in the delta rhythm and a decrease in theta and alpha rhythms were noted in lead C3-A1 compared to the control according to the rhythm index. After 6 months, the number of the supported rearing decreased in the Fe₃O₄AG 5000 group compared to the control group. In the remote period, a decrease in the average amplitude of delta and theta rhythms in lead Fp1-A1 in the experimental groups compared to the control group was more informative. The amplitude of the theta rhythm in the Fe₃O₄AG 500 group was also lower than in the Fe₃O₄AG 5000 group.

Limitations. The study was limited to examining behavioral responses in the «open field» and EEG parameters in male albino rats immediately after 10 days of administration of NC Fe₃O₄AG at doses of 500 µg/kg and 5000 µg/kg and a 6-month post-exposure period.

Conclusion. During the post-exposure period, NC Fe₃O₄AG at doses of 500 and 5000 µg/kg caused changes in behavioral responses and EEG in rats that were not dose-dependent, which requires further study.

Compliance with Ethical Standards. The study was approved by the local Ethics Committee of the East Siberian Institute of Medical and Ecological Research (ESIMER) (Conclusion No. 8 dated December 15, 2023) and was conducted in compliance with the international standards of the European Convention (ETS No. 123) and GLP requirements.

Contribution:
Yakimova N.L. – collection and processing of material, registration and description of EEG, writing text, editing;
Novikov M.A. – the concept and design of the study, implementation of animal studies, editing;
Skrynnik A.S. – collection and processing of material, and description of the results of the study of behavior;
Lizarev A.V. – collection of material, EEG registration, editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final version.

Acknowledgments. The authors express their gratitude to L.M. Sosedova, DSc (Medicine), professor, for consultative assistance and editing the article.

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

Funding. The study was carried out within the framework of a government assignment and had no additional sources of sponsorship.

Received: April 20, 2026 / Revised: July 10, 2026 / Accepted: September 15, 2026 / Published: October 20, 2026

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