Analysis of changes in the rat cardiovascular system under the action of lead intoxication and muscular exercise

Cover Page

Cite item

Full Text

Abstract

Introduction. One of the risk factors for cardiovascular diseases is the toxic metal pollution of the industrial area and the environment. Lead is the most critical of toxic metals. In industrial conditions, the body’s exposure to harmful substances is often combined with muscular work of varying severity. It has not been studied enough how these combinations influence the development of pathological processes associated with harmful exposure.

Materials and methods. The subchronic experiment was carried out on white outbred male rats for six weeks. Intoxication was simulated by repeated intraperitoneal injections of lead acetate three times a week. Running was chosen to model the muscle exercise at a 25 m/min speed for 10 minutes 5 days a week. We performed biochemical and electrocardiographic studies. Blood pressure parameters were recorded. Muscle contractility was studied on isolated multicellular preparations of the right ventricular myocardium in isometric and physiological contraction modes. The ratio of myosin heavy chains was determined by the polyacrylamide gel electrophoresis. The sliding velocity of reconstituted thin filaments on myosin using an in vitro motility assay. 

Results. Physical exercise under lead intoxication normalized the level of calcium and the angiotensin-converting enzyme activity in the blood serum, the voltage of the isoelectric line and the amplitude of the T wave on the electrocardiogram. The combined action of lead and physical exercise showed an increase in the creatinine kinase-MB level. We found that the effect of exercise under lead intoxication on myocardial contractility was ambiguous. The maximum isotonic shortening velocity in trabeculae was normalized, but the maximum rate of strength development in the isometric mode in the papillary muscles decreased to a greater extent than under lead intoxication. The maximum sliding velocity of reconstituted thin filaments and myosin and the heavy chain ratio was partly normalized. 

Conclusion. In general, muscle exercise attenuated the lead cardiotoxic effects.

Contribution:

Klinova S.V. — collection of literature data, collection and processing of material, writing a text;

Minigalieva I.A., Protsenko Yu.L., Nikitina L.V. — the concept and design of the study, editing;

Sutunkova M.P., Privalova L.I. — the concept and design of the study;

Ryabova Iu.V. — collection of literature data, collection and processing of material;

Gerzen O.P. — collection of literature data, writing a text;

Nabiev S.R., Balakin A.A., Lookin O.N., Lisin R.V., Kuznetsov D.A., Chernyshov I.N. — collection and processing of material;

Panov V.G. — statistical and mathematical processing;

Katsnelson L.B. — the concept and design of the study, writing a text, editing.

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 had no sponsorship.

Conclusion of the Local Ethics Committee of the Federal Service for Supervision of Consumer Rights Protection and Human Well-Being: Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers,of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing: keeping, feeding, caring for animals and removing them from the experiment was carried out in accordance with the requirements of the Declaration of Helsinki and “International guiding principles for biomedical research involving animals” developed by the Council for International Organizations of Medical Sciences and the International Council for Laboratory Animal Science (2012). The studies were approved by the Local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers,of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing (protocol No. 8 of 08.11.2018).

Received: October 19, 2021 / Accepted: November, 2021 / Published: December 30, 2021

About the authors

Svetlana V. Klinova

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

Author for correspondence.
Email: klinova.svetlana@gmail.com
ORCID iD: 0000-0002-0927-4062

Researcher, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers of Rospotrebnadzor, Yekaterinburg, 620014, Russian Federation.

e-mail: klinova.svetlana@gmail.com

Russian Federation

Ilzira A. Minigalieva

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-0097-7845
Russian Federation

Yuri L. Protsenko

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-4693-244X
Russian Federation

Marina P. Sutunkova

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1743-7642
Russian Federation

Iuliia V. Ryabova

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

Email: noemail@neicon.ru
ORCID iD: 0000-0003-2677-0479
Russian Federation

Oksana P. Gerzen

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

Email: noemail@neicon.ru
ORCID iD: 0000-0003-3853-1571
Russian Federation

Salavat R. Nabiev

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

Email: noemail@neicon.ru
ORCID iD: 0000-0001-9095-6775
Russian Federation

Alexander A. Balakin

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7712-6686
Russian Federation

Oleg N. Lookin

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

Email: noemail@neicon.ru
ORCID iD: 0000-0001-9544-1885
Russian Federation

Ruslan V. Lisin

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

Email: noemail@neicon.ru
ORCID iD: 0000-0001-6861-4816
Russian Federation

Daniil A. Kuznetsov

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

Email: noemail@neicon.ru
ORCID iD: 0000-0003-4519-3291
Russian Federation

Larisa I. Privalova

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-1442-6737
Russian Federation

Vladimir G. Panov

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Institute of Industrial Ecology, the Urals Branch of the Russian Academy of Sciences

Email: noemail@neicon.ru
ORCID iD: 0000-0001-6718-3217
Russian Federation

Ivan N. Chernyshov

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-2018-5386
Russian Federation

Leonid B. Katsnelson

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

Email: noemail@neicon.ru
ORCID iD: 0000-0001-9553-9110
Russian Federation

Larisa V. Nikitina

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

Email: noemail@neicon.ru
ORCID iD: 0000-0002-7174-2357
Russian Federation

Boris A. Katsnelson

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

Email: noemail@neicon.ru
ORCID iD: 0000-0001-8750-9624
Russian Federation

References

  1. Key scientific findings for lead (KSFfL). United Nations Environment Program; 2010. Avaliable at: https://wedocs.unep.org/bitstream/handle/20.500.11822/22871/Key_Scientific_Findings_Lead_EN.pdf
  2. Information and Technical Guide to the Best Available Technologies «ITS 13-2020 Production of Lead, Zinc and Cadmium» [Informatsionno-tekhnicheskiy spravochnik po nailuchshim dostupnym tekhnologiyam «ITS 13-2020 Proizvodstvo svintsa, tsinka i kadmiya»]. Moscow: Byuro NTD; 2020. (in Russian)
  3. State Report «On the State of Sanitary and Epidemiological Well-Being of the Population in the Russian Federation in 2019». Moscow; 2020. (in Russian)
  4. Trakhtenberg I.M., Lubyanova I.P., Apykhtina E.L. Lead and iron as man-made chemical pollutants in the pathogenesis of cardiovascular diseases. Meditsina profilakticheskaya. 2010; 49(7–8): 36–9. (in Russian)
  5. Alissa E.M., Ferns G.A. Heavy metal poisoning and cardiovascular disease. J. Toxicol. 2011; 2011: 870125. https://doi.org/10.1155/2011/870125
  6. Solenkova N.V., Newman J.D., Berger J.S., Thurston G., Hochman J.S., Lamas G.A. Metal pollutants and cardiovascular disease: mechanisms and consequences of exposure. Am. Heart J. 2014; 168(6): 812-22. https://doi.org/10.1016/j.ahj.2014.07.007
  7. Lamas G.A., Navas-Acien A., Mark D.B., Lee K.L. Heavy metals, cardiovascular disease, and the unexpected benefits of chelation therapy. J. Am. Coll. Cardiol. 2016; 67(20): 2411-8. https://doi.org/10.1016/j.jacc.2016.02.066
  8. Yang W.Y., Zhang Z.Y., Thijs L., Cauwenberghs N., Wei F.F., Jacobs L., et al. Left ventricular structure and function in relation to environmental exposure to lead and cadmium. J. Am. Heart Assoc. 2017; 6(2): e004692. https://doi.org/10.1161/JAHA.116.004692
  9. Institute for Health Metrics and Evaluation (IHME). GBD Compare. Seattle, WA: IHME, University of Washington; 2017. Avaliable at: https://vizhub.healthdata.org/gbd-compare
  10. Llerena F., Maynar M., Barrientos G., Palomo R., Robles M.C., Caballero M.J. Comparison of urine toxic metals concentrations in athletes and in sedentary subjects living in the same area of Extremadura (Spain). Eur. J. Appl. Physiol. 2012; 112(8): 3027-31. https://doi.org/10.1007/s00421-011-2276-6
  11. Maynar-Mariño M., Llerena F., Bartolomé I., Crespo C., Muñoz D., Robles M.C., et al. Effect of long-term aerobic, anaerobic and aerobic-anaerobic physical training in seric toxic minerals concentrations. J. Trace Elem. Med. Biol. 2018; 45: 136-41. https://doi.org/10.1016/j.jtemb.2017.10.007
  12. Roshan V.D., Assali M., Moghaddam A.H., Hosseinzadeh M., Myers J. Exercise training and antioxidants: effects on rat heart tissue exposed to lead acetate. Int. J. Toxicol. 2011; 30(2): 190-6. https://doi.org/10.1177/1091581810392809
  13. Shahandeh M., Roshan V.D., Hosseinzadeh S., Mahjoub S., Sarkisian V. Chronic exercise training versus acute endurance exercise in reducing neurotoxicity in rats exposed to lead acetate. Neural Regen. Res. 2013; 8(8): 714-22. https://doi.org/10.3969/j.issn.1673-5374.2013.08.006
  14. 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
  15. Gordon A.M., Homsher E., Regnier M. Regulation of contraction in striated muscle. Physiol. Rev. 2000; 80(2): 853-924. https://doi.org/10.1152/physrev.2000.80.2.853
  16. Shaffer J.F., Wong P., Bezold K.L., Harris S.P. Functional differences between the N-terminal domains of mouse and human myosin binding protein-C. J. Biomed. Biotechnol. 2010; 2010: 789798. https://doi.org/10.1155/2010/789798
  17. Laemmli U.K. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259): 680-5. https://doi.org/10.1038/227680a0
  18. Mashanov G.I., Molloy J.E. Automatic detection of single fluorophores in live cells. Biophys. J. 2007; 92(6): 2199-211. https://doi.org/10.1529/biophysj.106.081117
  19. Protsenko Y.L., Katsnelson B.A., Klinova S.V., Lookin O.N., Balakin A.A., Nikitina L.V., et al. Effects of subchronic lead intoxication of rats on the myocardium contractility. Food Chem. Toxicol. 2018; 120: 378-89. https://doi.org/10.1016/j.fct.2018.07.034
  20. Katsnelson B.A., Klinova S.V., Gerzen O.P., Balakin A.A., Lookin O.N., Lisin R.V., et al. Force-velocity characteristics of isolated myocardium preparations from rats exposed to subchronic intoxication with lead and cadmium acting separately or in combination. Food Chem. Toxicol. 2020; 144: 111641. https://doi.org/10.1016/j.fct.2020.111641
  21. Mast F., Elzinga G. Heat released during relaxation equals force length area in isometric contractions of rabbit papillary muscle. Circ. Res. 1990; 67(4): 893-901. https://doi.org/10.1161/01.res.67.4.893
  22. Myers R.H., Montgomery D.C., Anderson-Cook Ch.M. Response Surface Methodology: Process and Product Optimization Using Designed Experiments. (Wiley Series in Probability and Statistics). Hoboken, NJ: John Wiley & Sons Inc.; 2016.
  23. Rius R.A., Govoni S., Trabucchi M. Regional modification of brain calcium antagonist binding after in vivo chronic lead exposure. Toxicology. 1986; 40(2): 191-7. https://doi.org/10.1016/0300-483X(86)90078-8
  24. Lombardi G., Ziemann E., Banfi G., Corbetta S. Physical activity-dependent regulation of parathyroid hormone and calcium-phosphorous metabolism. Int. J. Mol. Sci. 2020; 21(15): 5388. https://doi.org/10.3390/ijms21155388
  25. Ferrara N. Role of vascular endothelial growth factor in the regulation of angiogenesis. Kidney Int. 1999: 56(3): 794-814. https://doi.org/10.1046/j.1523-1755.1999.00610.x
  26. Silveira E.A., Siman F.D., de Oliveira Faria T., Vescovi M.V., Furieri L.B., Lizardo J.H., et al. Low-dose chronic lead exposure increases systolic arterial pressure and vascular reactivity of rat aortas. Free Radic. Biol. Med. 2014; 67: 366-76. https://doi.org/10.1016/j.freeradbiomed.2013.11.021
  27. Carmignani M., Boscolo P., Poma A., Volpe A.R. Kininergic system and arterial hypertension following chronic exposure to inorganic lead. Immunopharmacol. 1999; 44(1-2): 105-10. https://doi.org/10.1016/S0162-3109(99)00115-0
  28. Sugiura S., Kobayakawa N., Fujita H., Yamashita H., Momomura S., Chaen S., et al. Comparison of unitary displacements and forces between 2 cardiac myosin isoforms by the optical trap technique. Molecular basis for cardiac adaptation. Circ. Res. 1998; 82(10): 1029-34. https://doi.org/10.1161/01.RES.82.10.1029
  29. Morgan J.P., Chesebro J.H., Pluth J.R., Puga F.J., Schaff H.V. Intracellular calcium transients in human working myocardium as detected with aequorin. J. Am. Coll. Cardiol. 1984: 3(2 Pt. 1): 410-8. https://doi.org/10.1016/S0735-1097(84)80028-5
  30. Klinova S.V., Minigalieva I.A., Privalova L.I., Valamina I.E., Makeyev O.H., Shuman E.A., et al. Further verification of some postulates of the combined toxicity theory: New animal experimental data on separate and joint adverse effects of lead and cadmium. Food Chem. Toxicol. 2020; 136: 110971. https://doi.org/10.1016/j.fct.2019.110971

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Klinova S.V., Minigalieva I.A., Protsenko Y.L., Sutunkova M.P., Ryabova I.V., Gerzen O.P., Nabiev S.R., Balakin A.A., Lookin O.N., Lisin R.V., Kuznetsov D.A., Privalova L.I., Panov V.G., Chernyshov I.N., Katsnelson L.B., Nikitina L.V., Katsnelson B.A.



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.