A novel approach to assessing cardiotoxic effects of nanoparticles in a toxicological experiment

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Introduction. The study of nanoparticles for potential cardiotoxic effects is a comprehensive multi-stage process based on an integrated approach. Along with generally accepted research methods, molecular biology techniques using modern highly sensitive equipment are being actively introduced into toxicology testing.

The aim of the study was to describe a novel approach to assessing cardiotoxic effects of nanoparticles, from the molecular level to the functional response of the whole organism.

Materials and methods. Our new approach to assessing cardiotoxic effects of nanoparticles in rats included the examination of changes at the molecular (e.g., the ratio of myosin heavy chains), subcellular (by electron microscopy), cellular and tissue (by histological testing), system and organ (by non-invasive recording of electrocardiogram and blood pressure parameters and biochemical testing of blood serum) levels. We have tested the proposed approach by evaluating lead (PBO) and cadmium oxide (CdO) nanoparticles in rats.

Results. Hypotension observed after PbO and/or CdO nanoparticle exposure indicates to the damage to the vascular bed due to penetration and accumulation of the nanoparticles in vascular cells, as well as direct damage to the endothelium, increased oxidative stress, and inflammation. In accordance with the system for assessing nanoparticle-induced cardiotoxicity developed on the basis of toxicology test results, lead and cadmium oxides, both separately and combined, have a pronounced cardiotoxic effect.

Limitations. Our work was limited to examining the main indicators of the cardiotoxic effects of nanoparticles in a toxicological experiment on one animal species (rats).

Conclusion. The data analysis revealed varying degrees of manifestation of nanoparticle cardiotoxicity, both at the molecular level and at the intracellular, cellular, tissue, organ, and body levels. The use of this approach will allow a better in-depth assessing effects of nano-sized particles on the heart and blood vessels for identification of risks for cardiovascular disease.

Compliance with ethical standards. The study was carried out in accordance with the ethical standards for the treatment of animals adopted by the European Convention for the Protection of Vertebrate Animals used Experimental and other Scientific Purposes. The study design was approved by the institutional Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 2 of April 20, 2021).

Contribution:
Klinova S.V. — study design, conducting the experiment, data collection and analysis, writing text, figure preparation;
Minigalieva I.A., Sutunkova M.P., Nikitina L.V. — study conception and design, scientific editing;
Valamina I.E., Shelomentsev I.G. — data collection and analysis, draft manuscript and figure preparation;
Gerzen O.P. — conducting the experiment, data collection and analysis;
Ryabova Yu.V., Shaikhova D.R. — conducting the experiment, data collection and analysis;
Mustafina I.Z., Orlov M.S. — scientific editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

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

Acknowledgement. The study of changes in the ratio of myosin heavy chains was carried out within the framework of the state. program No. 122022200089-4 (Institute of Immunology and Physiology Ural Branch RAS).

Received: April 19, 2024 / Accepted: September 23, 2024 / Published: October 16, 2024

Sobre autores

Svetlana Klinova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: klinova.svetlana@gmail.com

MD, PhD, DSci., head of the Laboratory of Industrial Toxicology, Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: klinova.svetlana@gmail.com

Ilzira Minigalieva

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: ilzira-minigalieva@yandex.ru

MD, PhD, DScl., head of the Department of Toxicology and Biological Prophylaxis, Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, Yekaterinburg, 620014, Russia

e-mail: ilzira-minigalieva@yandex.ru

Marina Sutunkova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural State Medical University

Email: sutunkova@ymrc.ru

MD, PhD, DSci. (Medicine), Director of the Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, 620014, Yekaterinburg,620014, Russian Federation; Associate Professor, Acting Head of the Department of Occupational Hygiene and Medicine, Ural State Medical University, Yekaterinburg, 620028, Russian Federation

e-mail: sutunkova@ymrc.ru

Irene Valamina

Ural State Medical University

Email: ivalamina@mail.ru

MD, PhD, Associate professor, head of the Histology Central Research Laboratory of the Ural State Medical University, Ekaterinburg, 620028, Russian Federation

e-mail: ivalamina@mail.ru

Oksana Gerzen

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Email: o.p.gerzen@gmail.com

MD, PhD, researcher, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, 620078, Russian Federation

e-mail: o.p.gerzen@gmail.com

Larisa Nikitina

Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences

Email: laranikita63@gmail.com

MD, PhD, DSci. (Biol.), leading researcher, Institute of Immunology and Physiology, Ural Branch of the Russian Academy of Sciences, Yekaterinburg, 620078, Russian Federation

e-mail: laranikita63@gmail.com

Yuliya Ryabova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: ryabovaiuvl@gmail.com

MD, PhD, head of Laboratory of Scientific Foundations of Biological Prophylaxis, Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ryabovaiuvl@gmail.com

Daria Shaikhova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: darya.boo@mail.ru

Researcher, Department of Molecular Biology and Electron Microscopy, Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: darya.boo@mail.ru

Ivan Shelomentsev

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Email: shelomencev@ymrc.ru

Researcher, Department of Molecular Biology and Electron Microscopy, Yekaterinburg Medical Research Center Prevention and Occupational Health of Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: shelomencev@ymrc.ru

Ilina Mustafina

Russian Medical Academy of Continuous Professional Education

Email: noemail@neicon.ru

PhD (Med.), head of the study section Russian Medical Academy of Continuous Professional Education, 125445, Moscow

Mihail Orlov

Russian Medical Academy of Continuous Professional Education

Autor responsável pela correspondência
Email: noemail@neicon.ru

PhD (Law), associate professor, section Russian Medical Academy of Continuous Professional Education, 125445, Moscow

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