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

Cover Page

Cite item

Full Text

Open Access Open Access
Restricted Access Access granted
Restricted Access Subscription Access

Abstract

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

About the authors

Svetlana V. 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 A. 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 P. 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 E. 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 P. 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 V. 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 V. 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 R. 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 G. 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 Z. 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 S. Orlov

Russian Medical Academy of Continuous Professional Education

Author for correspondence.
Email: noemail@neicon.ru

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

References

  1. WHO. Global Health Estimates: Life expectancy and leading causes of death and disability; 2019. Available at: https://who.int/data/gho/data/themes/mortality-and-global-health-estimates
  2. WHO. Reveals leading causes of death and disability worldwide: 2000–2019; 2020. Available at: https://who.int/news/item/09-12-2020-who-reveals-leading-causes-of-death-and-disability-worldwide-2000-2019
  3. Global health estimates: Leading causes of death. Cause-specific mortality, 2000–2021. Available at: https://who.int/data/gho/data/themes/mortality-and-global-health-estimates/ghe-leading-causes-of-death
  4. Ma W., He S., Xu Y., Qi G., Ma H., Bang J.J., et al. Ameliorative effect of sodium selenite on silver nanoparticles-induced myocardiocyte structural alterations in rats. Int. J. Nanomedicine. 2020; 15: 8281–92. https://doi.org/10.2147/IJN.S271457
  5. Toropova Ya.G., Osyaev N.Yu., Mukhamadiyarov R.A. Perfusion of the isolated heart by Langendorff and Neely methods: particular techniques and applications in recent scientific research. Translyatsionnaya meditsina. 2014; (4): 34–9. https://elibrary.ru/tsndtr (in Russian)
  6. Han J.C., Taberner A.J., Loiselle D.S., Tran K. Cardiac efficiency and Starling’s law of the heart. J. Physiol. 2022; 600(19): 4265–85. https://doi.org/10.1113/JP283632
  7. King D.R., Hardin K.M., Hoeker G.S., Poelzing S. Reevaluating methods reporting practices to improve reproducibility: an analysis of methodological rigor for the Langendorff whole heart technique. Am. J. Physiol. Heart Circ. Physiol. 2022; 323(3): H363–77. https://doi.org/10.1152/ajpheart.00164.2022
  8. Klinova S.V., Katsnelson B.A., Minigalieva I.A., Gerzen O.P., Balakin A.A., Lisin R.V., et al. Cardioinotropic effects in subchronic intoxication of rats with lead and/or cadmium oxide nanoparticles. Int. J. Mol. Sci. 2021; 22(7): 3466. https://doi.org/10.3390/ijms22073466
  9. Savi M., Bocchi L., Cacciani F., Vilella R., Buschini A., Perotti A., et al. Cobalt oxide nanoparticles induce oxidative stress and alter electromechanical function in rat ventricular myocytes. Part Fibre. Toxicol. 2021; 18(1): 1. https://doi.org/10.1186/s12989-020-00396-6
  10. Lin B.L., Li A., Mun J.Y., Previs M.J., Previs S.B., Campbell S.G., et al. Skeletal myosin binding protein-C isoforms regulate thin filament activity in a Ca2+-dependent manner. Sci. Rep. 2018; 8(1): 2604. https://doi.org/10.1038/s41598-018-21053-1
  11. Nikitina L.V., Kopylova G.V., Shchepkin D.V., Katsnelson L.B. Study of the interaction between rabbit cardiac contractile and regulatory proteins. An in vitro motility assay. Biochemistry (Mosc.). 2008; 73(2): 178–84. https://doi.org/10.1134/s0006297908020090
  12. Reiser P.J., Kline W.O. Electrophoretic separation and quantitation of cardiac myosin heavy chain isoforms in eight mammalian species. Am. J. Physiol. 1998; 274(3): H1048–53. https://doi.org/10.1152/ajpheart.1998.274.3.H1048
  13. Ansari M.A., Maayah Z.H., Bakheet S.A., El-Kadi A.O., Korashy H.M. The role of aryl hydrocarbon receptor signaling pathway in cardiotoxicity of acute lead intoxication in vivo and in vitro rat model. Toxicology. 2013; 306: 40–9. https://doi.org/10.1016/j.tox.2013.01.024
  14. Urbakh V.Yu., Polunina O.S., Sevost’yanova I.V., Voronina L.P. Biometric Methods [Biometricheskie metody]. Moscow: Nauka; 1964. (in Russian)
  15. Arian M., Soleimani M. Practical calculation of mean, pooled variance, variance, and standard deviation, in meta-analysis studies. Nurs. Pract. Today. 2020; 7(1): 5–11. https://doi.org/10.18502/npt.v7i1.2294
  16. Elgharabawy R.M., Alhowail A.H., Emara A.M., Aldubayan M.A., Ahmed A.S. The impact of chicory (Cichoriumintybus L.) on hemodynamic functions and oxidative stress in cardiac toxicity induced by lead oxide nanoparticles in male rats. Biomed. Pharmacother. 2021; 137: 111324. https://doi.org/10.1016/j.biopha.2021.111324
  17. Sutunkova M.P., Minigalieva I.A., Klinova S.V., Panov V.G., Gurvich V.B., Privalova L.I., et al. Some data on the comparative and combined toxic activity of nanoparticles containing lead and cadmium with special attention to their vasotoxicity. Nanotoxicology. 2021; 15(2): 205–22. https://doi.org/10.1080/17435390.2020.1845410
  18. Ohno A., Naruse M., Kato S., Hosaka M., Naruse K., Demura H., et al. Endothelin-specific antibodies decrease blood pressure and increase glomerular filtration rate and renal plasma flow in spontaneously hypertensive rats. J. Hypertens. 1992; 10(8): 781–5.
  19. Simões M.R., Ribeiro R.F. Jr., Vescovi M.V., de Jesus H.C., Padilha A.S., Stefanon I., et al. Acute lead exposure increases arterial pressure: role of the renin-angiotensin system. PLoS One. 2011; 6(4): e18730. https://doi.org/10.1371/journal.pone.0018730
  20. Sharifi A.M., Darabi R., Akbarloo N., Larijani B., Khoshbaten A. Investigation of circulatory and tissue ACE activity during development of lead-induced hypertension. Toxicol. Lett. 2004; 153(2): 233–8. https://doi.org/10.1016/j.toxlet.2004.04.013
  21. Zhou J., Allen A.M., Yamada H., Sun Y., Mendelsohn F.A.O. Localization and properties of angiotensin converting enzyme and angiotensin receptors in the heart. In: Lindpaintner K., Ganten D., eds. The Cardiac-Renin Angiotensin System. Armonk, NY: Futura; 1994: 63–88.
  22. Potter L.R., Abbey-Hosch S., Dickey D.M. Natriuretic peptides, their receptors, and cyclic guanosine monophosphate-dependent signaling functions. Endocr. Rev. 2006; 27(1): 47–72. https://doi.org/10.1210/er.2005-0014
  23. Polunina E.A., Polunina O.S., Sevost’yanova I.V., Voronina L.P. «Multifunctional» C-type natriuretic peptide and its discussion/advanced research in chronic heart failure. Astrakhanskii meditsinskii zhurnal. 2017; 12(3): 28–37. https://elibrary.ru/zvrcgd (in Russian)
  24. Fu P.P., Xia Q., Hwang H.M., Ray P.C., Yu H. Mechanisms of nanotoxicity: generation of reactive oxygen species. Journal of Food and Drug Analysis. 2014; 22(1): 64–75. https://doi.org/10.1016/j.jfda.2014.01.005
  25. Cheng Y., Chen Z., Yang S., Liu T., Yin L., Pu Y., et al. Nanomaterials-induced toxicity on cardiac myocytes and tissues, and emerging toxicity assessment techniques. Sci. Total Environ. 2021; 800: 149584. https://doi.org/10.1016/j.scitotenv.2021.149584
  26. Panov V., Minigalieva I., Bushueva T., Fröhlich E., Meindl C., Absenger-Novak M., et al. Some peculiarities in the dose dependence of separate and combined in vitro cardiotoxicity effects induced by CdS and PbS nanoparticles with special attention to hormesis manifestations. Dose Response. 2020; 18(1): 1559325820914180. https://doi.org/10.1177/1559325820914180
  27. Scheffler T.L., Leitner M.B., Wright S.A. Technical note: Protocol for electrophoretic separation of bovine myosin heavy chain isoforms and comparison to immunohistochemistry analysis. J. Anim. Sci. 2018; 96(10): 4306–12. https://doi.org/10.1093/jas/sky283

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2025


СМИ зарегистрировано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).
Регистрационный номер и дата принятия решения о регистрации СМИ: серия ПИ № ФС 77 - 37884 от 02.10.2009.