Evaluation of toxic effects of magnetic contrast diagnostic gadolinium-containing nanocomposite

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Abstract

Introduction. In recent years, magnetic nanoparticles, which can simultaneously have a therapeutic effect on the pathological focus, are used to magnify contrast enhancement and increase diagnostic sensitivity during magnetic resonance therapy (MRT). The last is carried out by the effective capture of neutrons, which among all the chemical elements is most pronounced in gadolinium. The use of gadolinium nanoparticles encapsulated in a polymeric matrix allows increasing the bioavailability of nanoparticles, reduces the possible toxicity of drugs.

Aim. Evaluation of impact of new nanocomposite magnetically active metal complex gadolinium system on the morphofunctional state of the nervous tissue, liver, and kidney of rats.

Material and methods. Experimental studies of biological effects of gadolinium-arabinogalactan nanocomposite (Gd-AG) were carried out on rats that were injected intraperitoneally for 10 days at the dose of 500 μg/kg in 0.5 ml of saline. Animals were sacrificed by decapitation under light ether anesthesia the next day after the end of exposure. To perform pathological studies, frontal sections of the temporal-parietal zone of the sensorimotor cortex, liver and kidney tissues were stained on ordinary histological glass slides with hematoxylin and eosin for viewing microscopic picture. The immunohistochemical method was used to determine the activity of the bcl-2, caspase-3 and hsp70 modulatory protein in apoptosis of white rats in brain neurons and to study the biological response of the organism at the subcellular level.

Results. Histological analysis of tissues revealed a pronounced compensatory response of liver, a violation of the functional activity of kidneys. A decrease in the total number of normal neurons per unit area in brain tissue and an increase in the number of acts of neuronophagy indicate the initial stage of neurodegenerative process. Evaluation of the intracellular metabolism of neurons has not established the presence of signs characteristic of apoptotic process.

Conclusion. The subacute effect of Gd-AG in a dose of 500 µg/kg causes a disturbance of morphofunctional state of liver, kidneys and nervous tissue, as well as modulation of cellular proteomics.

About the authors

Larisa M. Sosedova

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Author for correspondence.
Email: sosedlar@mail.ru
ORCID iD: 0000-0003-1052-4601

MD, Ph.D., DSci., Professor, Head of Laboratory of biomodeling and translational medicine of the East-Siberian Institute of Medical and Ecological Research, Angarsk, 665827, Russian Federation.

e-mail: sosedlar@mail.ru

Russian Federation

E. A. Titov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0002-0665-8060
Russian Federation

M. A. Novikov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0002-6100-6292
Russian Federation

V. A. Vokina

East-Siberian Institute of Medical and Ecological Research

Email: noemail@neicon.ru
ORCID iD: 0000-0002-8165-8052
Russian Federation

V. S. Rukavishnikov

East-Siberian Institute of Medical and Ecological Research; Irkutsk Scientific Center Siberian Branch of Russian Academy of Science

Email: noemail@neicon.ru
ORCID iD: 0000-0003-2536-1550
Russian Federation

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Copyright (c) 2019 Sosedova L.M., Titov E.A., Novikov M.A., Vokina V.A., Rukavishnikov V.S.


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