Assessment of neurotoxicity of gadolinium nanocomposite

Introduction. A promising area of nanotoxicology is the study of the effects of gadolinium nanoparticles on a living organism, which will allow achieving high image contrast when performing MRI with a significantly smaller amount of the injected substance. This is possible using high-molecular compounds, for example, arabinogalactan of Siberian larch, which has a stabilizing effect for nanoparticles.

Materials and methods. Experimental studies were performed on ninety six mongrel white male rats weighing 180–240 g, divided into 3 groups (one control and two experimental). A water-based solution was used as the exposed substance, which included gadolinium nanoparticles, as well as a nanostabilizing matrix – the natural polysaccharide arabinogalactan. The solution was administered orally for 10 days in two doses – 500 and 5000 mcg of gadolinium per 1 kg of animal body weight. After the introduction, some of the animals were withdrawn from the experiment and made up the early examination period, the remaining part of the animals were left to survive for 6 months and made up the long-term examination period, and subsequently were also withdrawn from the experiment. The work used a set of studies aimed at determining neurotoxicity – the “Open Field” test, EEG examination, morphological and morphometric methods.

Results. The structural and functional features of the effect of gadolinium nanocomposite on the central nervous system were expressed in an increase in the number of degeneratively altered neurons when administered a solution at a dose of 500 mcg of gadolinium per 1 kg of animal body weight in the early period of examination, while indices reflecting approximate research activity, behaviour and EEG indices, compared with the control, did not changed.

Limitations. When studying the effects of gadolinium nanoparticles encapsulated in the polysaccharide arabinogalactan on 96 outbred male rats, which is sufficient to use a set of methods to determine the functional state of the central nervous system and structural changes in nervous tissue.

Conclusion. Thus, the subacute effect of gadolinium nanoparticles encapsulated in the arabinogalactan matrix causes structural changes in the nervous tissue, while functional changes in the central nervous system were not observed.

Compliance with ethical standards. The work was carried out in accordance with the protocol of experimental studies, the principles set out in the European Convention for the Protection of Vertebrate Animals used for Experimental and Other Scientific Purposes ETS No. 123, GOST 33215–2014 “Guide to the care and maintenance of laboratory animals. Rules for equipping premises and organizing procedures», Recommendations for euthanasia of experimental animals: Part 1, Part 2. Permission to conduct the research was obtained from the Local Ethics Committee (protocol No. 8 dated 15.12.2023).

Contribution:
Novikov M.A., Sosedova L.M. — study concept and design, writing text, editing;
Titov E.A., Vokina V.A. — study concept and design, editing;
Yakimova N.L., Pankova A.A., Skrynnik A.S., Lizarev A.V. — data collection and data processing.
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.

Acknowledgement. The study was carried out within the framework of the state assignment of the East Siberian Institute of Medical and Ecological Research.

Received: July 8, 2024 / Revised: October 15, 2024 / Accepted: November 19, 2024 / Published: December 17, 2024