Experimental study of the combined effect of benzene exposure and physical load in rats
- Authors: Minigalieva I.A.1, Shabardina L.V.1, Ryabova Y.V.1, Nikogosyan K.M.1, Panov V.G.1,2, Sutunkova M.P.1,3, Sakhautdinova R.R.1
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Affiliations:
- Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
- Institute of Industrial Ecology, Ural Branch of the Russian Academy of Sciences
- Ural State Medical University
- Issue: Vol 104, No 1 (2025)
- Pages: 101-109
- Section: PREVENTIVE TOXICOLOGY AND HYGIENIC STANDARTIZATION
- Published: 15.12.2025
- URL: https://rjsocmed.com/0016-9900/article/view/655520
- DOI: https://doi.org/10.47470/0016-9900-2025-104-1-101-109
- EDN: https://elibrary.ru/qzvrne
- ID: 655520
Cite item
Abstract
Introduction. The working process in many industries is often associated not only with chemical exposures but also with heavy physical workload, which can be potent of toxic effects of the former differently.
The purpose of the study was to establish body responses to effects of benzene exposure combined with exercise in an experiment on rats.
Materials and methods. The study was conducted on mature male Wistar rats, ten animals in each of the following groups: “Control”, “Running”, “Benzene exposure”, and “Benzene exposure + running”. Subchronic toxicity was modelled by intragastric administration of benzene thrice a week for 4 weeks in a cumulative dose of 100 mg/kg body weight. Exercise was modelled by means of 10-minute forced running sessions at a speed of 25 m/min 5 times a week for 4 weeks. We then measured post-exposure biochemical and hematological indices and the proportion of different types of cells in imprint smears of rat internal organs. Statistical data analysis was carried out using the Student’s t-test with p<0.05. For mathematical modelling of the combined effect of factors, we applied a Response Surface Method (RSM) with the construction of Loewe isobols on its basis.
Results. Almost no statistically significant changes were registered in the rodents who exercised while statistical ones were sporadic and diagnostically insignificant in most cases. Benzene exposure induced changes in blood indices indicating blood clotting disorders, typical of chronic exposure to benzene, and in the antioxidant system. The impact of running on health effects of benzene exposure was ambiguous but isobolographic analysis showed possible additivity and even synergy, both detrimental to health, in 15.6 % of cases.
Limitations. Extrapolation of the study results to human should be done with caution, since the combined effect has been examined only for subchronic exposure using a single species and sex of laboratory animals.
Conclusion. Additivity proven by a number of indices of toxic effect gives important information for understanding and predicting health effects of exposure to organic pollutants combined with physical activity.
Compliance with ethical standards. This experimental study was approved by the institutional Bioethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 2 of January 11, 2024).
Contribution:
Minigalieva I.A. – study conception and design, editing;
Shabardina L.V. – data collection and analysis, draft manuscript preparation;
Ryabova Yu.V. – draft manuscript preparation, editing;
Nikogosyan K.M. – data collection;
Panov V.G. – data analysis;
Sutunkova M.P. – editing, study conception and design;
Sakhautdinova R.R. – data collection and analysis.
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.
Received: April 23, 2024 / Revised: May 21, 2024 / Accepted: June 19, 2024 / Published: January 31, 2025
Keywords
About the authors
Ilzira A. Minigalieva
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Email: noemail@neicon.ru
DSc (Biology), Head of the Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
Lada V. Shabardina
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Email: lada.shabardina@mail.ru
Junior researcher, Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
e-mail: lada.shabardina@mail.ru
Yuliya V. Ryabova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Email: noemail@neicon.ru
PhD (Medicine), Head of the Laboratory of Scientific Foundations of Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
Karen M. Nikogosyan
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Email: noemail@neicon.ru
Junior Researcher, Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
Vladimir G. Panov
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Institute of Industrial Ecology, Ural Branch of the Russian Academy of Sciences
Email: noemail@neicon.ru
PhD (Physics&Mathematics), Senior Researcher, Department of Toxicology and Bioprophylaxis, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
Marina P. Sutunkova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural State Medical University
Email: noemail@neicon.ru
DSc (Medicine), Director, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
Renata R. Sakhautdinova
Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers
Author for correspondence.
Email: noemail@neicon.ru
PhD (Medicine), Head of the Department of Laboratory Diagnostics, Research and Production Department “Laboratory and Diagnostic Technologies”, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation
References
- ATSDR. Agency for Toxic Substances and Disease Registry; 2024. Available at: https://atsdr.cdc.gov/index.html
- IARC. International Agency for Research on Cancer. IARC Monographs Volume 120: Benzene; 2018. Available at: https://iarc.who.int/news-events/iarc-monographs-volume-120-benzene/
- Arnold S.M., Angerer J., Boogaard P.J., Hughes M.F., O’Lone R.B., Robison S.H., et al. The use of biomonitoring data in exposure and human health risk assessment: benzene case study. Crit. Rev. Toxicol. 2013; 43(2): 119–53. https://doi.org/10.3109/10408444.2012.756455
- Snyder R. Leukemia and benzene. Int. J. Environ. Res. Public Health. 2012; 9(8): 2875–93. https://doi.org/10.3390/ijerph9082875
- Sun R., Xu K., Ji S., Pu Y., Yu L., Yin L., et al. Toxicity in hematopoietic stem cells from bone marrow and peripheral blood in mice after benzene exposure: Single-cell transcriptome sequencing analysis. Ecotoxicol. Environ. Saf. 2021; 207: 111490. https://doi.org/j.ecoenv.2020.111490
- Klinova S.V., Minigalieva I.A., Protsenko Y.L., Sutunkova M.P., Gurvich V.B., Ryabova J.V., et al. Changes in the cardiotoxic effects of lead intoxication in rats induced by muscular exercise. Int. J. Mol. Sci. 2022; 23(8): 4417. https://doi.org/10.3390/ijms23084417
- 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
- Rusin M.N., Amirov N.Kh., Sibgatullin A.S., Krasnoshchekova V.N. Health status of electrotechnical personnel exposed to the combined impact of electromagnetic fields of 50 Hz and chemicals. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2015; 94(3): 52–5. https://elibrary.ru/twelxp (in Russian)
- Panov V.G., Varaksin A.N. Identification of combined action types in experiments with two toxicants: a response surface linear model with a cross term. Toxicol. Mech. Methods. 2016; 26(2): 139–50. https://doi.org/10.3109/15376516.2016.1139023
- Kutafina N.V., Medvedev I.N. The influence of physical exercise on the hemostasis system. Vestnik Surgutskogo gosudarstvennogo pedagogicheskogo universiteta. 2014; (3): 87–91. https://elibrary.ru/zbknkx (in Russian)
- Kalinkin L.A., Statsenko E.A., Ponomareva A.G., Morozov V.N., Kutnyakhova L.V., Krivoshchapov M.V., et al. Oxidative stress while physical activity: methods of evaluation and correction of antioxidant status. Vestnik sportivnoi nauki. 2014; (1): 31–5. https://elibrary.ru/szxsqt (in Russian)
- Sakhautdinova R.R., Ryabova Yu.V., Panov V.G., Minigalieva I.A., Sutunkova M.P., Bushueva T.V. Application of imprint cytology in assessment of immunological effects of isolated and combined action of selenium and copper nanoparticles. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2021; 100(12): 1502–7. https://doi.org/10.47470/0016-9900-2021-100-12-1502-1507 https://elibrary.ru/hyppyr (in Russian)
- Sutunkova M.P., Solovyeva S.N., Minigalieva I.A., Gurvich V.B., Valamina I.E., Makeyev O.H., et al. Toxic effects of low-level long-term inhalation exposures of rats to nickel oxide nanoparticles. Int. J. Mol. Sci. 2019; 20(7): 1778. https://doi.org/10.3390/ijms20071778
- Orujov R.A., Dzhafarova R.E. Changes in the nervous system state and peripheral blood parameters under benzene intoxication during an experiment. Health Risk Analysis. 2017; (4): 108–16. https://doi.org/10.21668/health.risk/2017.4.12.eng https://elibrary.ru/nhhocn
- Sun R., Zhang J., Wei H., Meng X., Ding Q., Sun F., et al. Acetyl-l-carnitine partially prevents benzene-induced hematotoxicity and oxidative stress in C3H/He mice. Environ. Toxicol. Pharmacol. 2017; 51: 108–13. https://doi.org/10.1016/j.etap.2017.02.013
- Cui Y., Mo Z., Ji P., Zhong J., Li Z., Li D., et al. Benzene exposure leads to lipodystrophy and alters endocrine activity in vivo and in vitro. Front. Endocrinol. (Lausanne). 2022; 13: 937281. https://doi.org/10.3389/fendo.2022.937281
- Sharapova N.V., Petrova A.A., Karmanova D.S., Krasikov S.I. The effect of non-toxic doses of benzene on blood lipid profile in the experiment. Vestnik novykh meditsinskikh tekhnologii. 2019; 26(1): 104–7. https://doi.org/10.24411/1609-2163-2019-16332 https://elibrary.ru/vxdkbj (in Russian)
- Wang J., Guo X., Chen Y., Zhang W., Ren J., Gao A. Association between benzene exposure, serum levels of cytokines and hematological measures in Chinese workers: A cross-sectional study. Ecotoxicol. Environ. Saf. 2021; 207: 111562. https://doi.org/10.1016/j.ecoenv.2020.111562
- Schlosser P.M., Bond J.A., Medinsky M.A. Benzene and phenol metabolism by mouse and rat liver microsomes. Carcinogenesis. 1993; 14(12): 2477–86. https://doi.org/10.1093/carcin/14.12.2477
- Mikhailova I.V., Smolyagin A.I., Krasikov S.I., Karaulov A.V. Impact of benzene on the immune system and some of the mechanisms of its action. Immunologiya. 2014; 35(1): 51–6. https://elibrary.ru/ryxxbb (in Russian)
- Neghab M., Hosseinzadeh K., Hassanzadeh J. Early liver and kidney dysfunction associated with occupational exposure to sub-threshold limit value levels of benzene, toluene, and xylenes in unleaded petrol. Saf. Health Work. 2015; 6(4): 312–6. https://doi.org/10.1016/j.shaw.2015.07.008
- Minigalieva I.A., Katsnelson B.A., Privalova L.I., Sutunkova M.P., Gurvich V.B., Shur V.Y., et al. Combined subchronic toxicity of aluminum (III), titanium (IV) and silicon (IV) oxide nanoparticles and its alleviation with a complex of bioprotectors. Int. J. Mol. Sci. 2018; 19(3): 837. https://doi.org/10.3390/ijms1903083
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