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

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