Attenuation of adverse effects of lead exposure against background of the physical load in a subchronic experiment

Introduction. Occupational lead exposure poses danger due to large economic losses mainly associated with a decrease in working life expectancy. It is common knowledge that physical activity, which is inherent to working conditions in metallurgy, can affect poisoning in different ways, including enhancing it.

Objective. To substantiate and test a bioprophylactic complex (BPC) aimed at increasing the resistance of the organism to moderate lead intoxication combined with moderate physical activity in an animal experiment.

Materials and methods. Lead poisoning was modeled on outbred male rats by intraperitoneal administration of lead acetate to the exposure groups in a total dose of 198 mg/kg body weight during 6 weeks. Control animals received saline in a similar volume. Physical activity was modeled using a small rodent treadmill. Some animals were also administered a special BPC which included the following components: enterosorbent – apple pectin, membrane stabilizer – glutamic acid, lead antagonist calcium in combination with vitamin D3, magnesium, potassium, iodine, and some antioxidants – Omega-3, vitamin C, rutin, acetylcysteine, and others.

Results. Physical exercise itself did not affect the parameters under study but aggravated toxic effects of lead when combined: anemia worsened and, the proportion of abnormal spermatozoa rose (without a decrease in their viability, however). Administration of the bioprophylactic complex mitigated the adverse effects mentioned above.

Limitations. The study was limited to using laboratory animals of the same sex and age.

Conclusion. The developed complex can serve as an auxiliary tool aimed at reducing health risks to individuals occupationally exposed to lead compounds and physical work.

Compliance with ethical standards. The experiment was approved by the local Bioethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No.8 of 27.02.2020).

Contribution:
Minigalieva I.A. — data analysis, draft manuscript preparation, editing;
Sutunkova M.P. — study conception and design;
Nikogosyan K.M. — data collection, draft manuscript preparation, 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.

Funding. The study had no sponsorship.

Received: June 17, 2025 / Revised: July 17, 2025 / Accepted: October 15, 2025 / Published: November 14, 2025

1. State report «On the state of sanitary and epidemiological well-being of the population in the Russian Federation in 2022». Moscow; 2023. (in Russian)

2. Klinova S.V., Minigalieva I.A., Sutunkova M.P., Shabardina L.V. Integral indicators of cardiotoxicity of lead and cadmium on the background of physical activity. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2023; 102(11): 1228–35. https://doi.org/10.47470/0016-9900-2023-102-11-1228-1235 https://elibrary.ru/nunamk (in Russian)

3. Shabardina L.V., Ryabova Yu.V., Klinova S.V., Sutunkova Yu.M. Effects of combined action of cadmium and physical load on the hematological blood parameters of rats. In: Current Issues of Modern Medical Science and Healthcare: Collection of Articles of the VIII International Scientific and Practical Conference of Young Scientists and Students [Aktual’nye voprosy sovremennoi meditsinskoi nauki i zdravookhraneniya: sbornik statei VIII Mezhdunarodnoi nauchno-prakticheskoi konferentsii molodykh uchenykh i studentov]. Ekaterinburg; 2023: 956–62. (in Russian)

4. Beckwith T.J., Dietrich K.N., Wright J.P., Altaye M., Cecil K.M. Reduced regional volumes associated with total psychopathy scores in an adult population with childhood lead exposure. Neurotoxicology. 2018; 67: 1–26. https://doi.org/10.1016/j.neuro.2018.04.004

5. Chen Z., Huo X., Zhang S., Cheng Z., Huang Y., Xu X. Relations of blood lead levels to echocardiographic left ventricular structure and function in preschool children. Chemosphere. 2021; 268: 128793. https://doi.org/10.1016/j.chemosphere.2020.128793

6. Baranowska-Bosiacka I., Kosińska I., Jamioł D., Gutowska I., Prokopowicz A., Rębacz-Maron E., et al. Environmental lead (Pb) exposure versus fatty acid content in blood and milk of the mother and in the blood of newborn children. Biol. Trace Elem. Res. 2016; 170(2): 279–87. https://doi.org/10.1007/s12011-015-0482-5

7. Fadrowski J.J., Abraham A.G., Navas-Acien A., Guallar E., Weaver V.M., Furth S.L. Blood lead level and measured glomerular filtration rate in children with chronic kidney disease. Environ. Health Perspect. 2013; 121(8): 965–70. https://doi.org/10.1289/ehp.1205164

8. Goldstein S.L. Acute kidney injury in children and its potential consequences in adulthood. Blood Purif. 2012; 33(1–3): 131–7. https://doi.org/10.1159/000334143

9. Katsnelson B.A., Privalova L.I., Gurvich V.B., Kuzmin S.V., Kireyeva E.P., Minigalieva I.A., et al. The role of bio-prevention in the framework of managing occupational and environmental chemical risks to population health. Toksikologicheskii vestnik. 2015; (1): 10–21. https://elibrary.ru/lbmspr (in Russian)

10. Ryabova Yu.V., Klinova S.V., Chernyshov I.N. Positive effect of bioprophylaxis in terms of rat spermatogenesis during subchronic intoxication with lead and cadmium oxides by nanoparticles. Meditsina truda i ekologiya cheloveka 2019; (4): 59–67. https://elibrary.ru/wyjwao (in Russian)

11. Ryabova Yu.V., Nikogosyan K.M., Bateneva V.A. Methods of increasing cell resistance to the cytotoxic effects of factors in the production environment and habitat as the basis for preventive effects. In: Collection of Articles and Theses. Medical Science: Yesterday, Today, Tomorrow [Sbornik ctatei i tezisov. Meditsinskaya nauka: vchera, segodnya, zavtra]. Moscow: Triton; 2024. (in Russian)

12. Wani A.L., Ara A., Usmani J.A. Lead toxicity: a review. Interdiscip. Toxicol. 2015; 8(2): 55–64. https://doi.org/10.1515/intox-2015-0009

13. Schuschkevich N.I. Impact of the lead on the blood parameters of the workers leaden production. Vestnik Rossiiskogo universiteta druzhby narodov. Seriya: Ekologiya i bezopasnost’ zhiznedeyatel’nosti. 2007; (1): 49–53. https://elibrary.ru/ijeycr (in Russian)

14. Kireyeva Ye.P., Kalsnelson B.A., Degtyaryova T.D., Privalova L.I., Valamina L.Ye., Beresneva O.Yu., et al. Nephrotoxic effect posed by lead and cadmium and its inhibition by a complex of bioproteetive agents. Toksikologicheskii vestnik. 2006; (3): 26–32. https://elibrary.ru/htvild (in Russian)

15. Jaffe E.K., Martins J., Li J., Kervinen J., Dunbrack R.L. Jr. The molecular mechanism of lead inhibition of human porphobilinogen synthase. J. Biol. Chem. 2001; 276(2): 1531–7. https://doi.org/10.1074/jbc.M007663200

16. Al Momen A. Thrombocytosis secondary to chronic lead poisoning. Platelets. 2010; 21(4): 297–9. https://doi.org/10.3109/09537101003612813

17. 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

18. Metryka E., Chibowska K., Gutowska I., Falkowska A., Kupnicka P., Barczak K., et al. Lead (Pb) exposure enhances expression of factors associated with inflammation. Int. J. Mol. Sci. 2018; 19(6): 1813. https://doi.org/10.3390/ijms19061813

19. Gorkhali R., Huang K., Kirberger M., Yang J.J. Defining potential roles of Pb(2+) in neurotoxicity from a calciomics approach. Metallomics. 2016; 8(6): 563–78. https://doi.org/10.1039/c6mt00038j

20. Gavazzo P., Zanardi I., Baranowska-Bosiacka I., Marchetti C. Molecular determinants of Pb2+ interaction with NMDA receptor channels. Neurochem. Int. 2008; 52(1–2): 329–37. https://doi.org/10.1016/j.neuint.2007.07.003

21. Bitto E., Bingman C.A., Wesenberg G.E., McCoy J.G., Phillips G.N. Jr. Structure of pyrimidine 5’-nucleotidase type 1. Insight into mechanism of action and inhibition during lead poisoning. J. Biol. Chem. 2006; 281(29): 20521–9. https://doi.org/10.1074/jbc.M602000200

22. Kitikova N.V., Polovinkin L.V., Ushkov A.A., Shishkova I.L., Rat’ko A.I., Polovinkina T.I., et al. Corrective effect of drugs calcium phosphates during experimental lead intoxication. Toksikologicheskii vestnik. 2006; (1): 12–6. https://elibrary.ru/wdsfyl (in Russian)

23. Skoczyńska A., Wojakowska A., Nowacki D., Bobak Ł., Turczyn B., Smyk B., et al. Unsaturated fatty acids supplementation reduces blood lead level in rats. Biomed. Res. Int. 2015; 2015: 189190. https://doi.org/10.1155/2015/189190

24. Cao X.J., Cao J.J., Chen T.T., Chen W.H., Ruan D.Y. Protective effects of omega-3 fish oil on lead-induced impairment of long-term potentiation in rat dentate gyrus in vivo. Sheng Li Xue Bao. 2010; 62(3): 225–30.

25. Ahmad F., Liu P. (Ascorb)ing Pb neurotoxicity in the developing brain. Antioxidants (Basel). 2020; 9(12): 1311. https://doi.org/10.3390/antiox9121311

26. Sutunkova M.P., Minigalieva I.A., Panov V.G., Riabova I.V., Privalova L.I., Katsnelson B.A., et al. Multisystemic damage to mitochondrial ultrastucture as an integral measure of the comparative in vivo cytotoxicity of metallic nanoparticles. IOP Conf. Ser.: Mater. Sci. Eng. 2020; 918. https://doi.org/10.1088/1757-899X/918/1/012119 https://elibrary.ru/wnacmp

27. Alexander J., Aaseth J., Mikalsen A. Excretion of lead in rat bile – the role of glutathione. Acta Pharmacol. Toxicol. (Copenh). 1986; 59(Suppl. 7): 486–9. https://doi.org/10.1111/j.1600-0773.1986.tb02809.x

28. Ahmad F., Haque S., Ravinayagam V., Ahmad A., Kamli M.R., Barreto G.E., et al. Developmental lead (Pb)-induced deficits in redox and bioenergetic status of cerebellar synapses are ameliorated by ascorbate supplementation. Toxicology. 2020; 440: 152492. https://doi.org/10.1016/j.tox.2020.152492

29. Katsnelson B.A., Degtyareva T.D., Privalova L.I. Principles of Biological Prevention of Occupational and Environmentally Caused Pathologies from Exposure to Inorganic Substances [Printsipy biologicheskoi profilaktiki professional’noi i ekologicheski obuslovlennoi patologii ot vozdeistviya neorganicheskikh veshchestv]. Ekaterinburg; 1999. (in Russian