Neurotoxic effects of cadmium chloride exposure combined with physical activity and protective effect of bioprophylactic agents

Cover Page

Cite item

Full Text

Abstract

Introduction. Chemical compounds possessing of a neurotropic effect are extremely widespread in industry, which makes the problem of neurotoxicity relevant for occupational medicine. Since industrial workers are often exposed to a combination of both physical and chemical work-related risk factors, a complex adverse health effect of the latter should be considered.

Our objective was to study neurotoxic effects of exposure to cadmium chloride combined with physical activity in a subchronic experiment on rats and assess the efficacy of a biological prophylactic complex.

Material and methods. For six weeks, 0.77 mg/kg b.w. of cadmium chloride was intraperineally instilled to outbred male albino rats thrice a week. Five times a week, the rodents were forced to run for 10 minutes at a speed of 25 m/min. During the entire exposure period, half of the animals received a specially developed bioprophylactic complex consisting of pectin, monosodium glutamate, and a multivitamin/multimineral supplement with feed and drink.

Results. In combination with physical activity, cadmium exposure caused depression, anxiety, low exploratory behaviour, and spatial memory disturbances. The developed bioprophylactic complex helped mitigate toxic effects of cadmium aggravated with intense physical activity and improve the general condition of the rodents.

Limitations. The experiment was limited to examining the behaviour of male rats following subchronic exposure to a single dose of cadmium.

Conclusions. Subchronic exposure to cadmium combined with physical activity can induce certain neurotoxic effects. Administration of the specially developed complex of biological protectors has shown to attenuate or minimize these effects. Similar measures can be taken to diminish risks of adverse health consequences of the factors studied.

Compliance with ethical standards. The study was carried out in accordance with ethical principles for the treatment of animals adopted by the European Convention for the Protection of Vertebrate Animals Used for Experiments and Other Scientific Purposes (ETS 123). The study protocol was approved by the Local Independent Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 4 of September 30, 2022).

Contribution:
Ryabova Yu.V. — study conception and design, draft manuscript preparation;
Shabardina L.V. — data collection and analysis, draft manuscript preparation;
Keskevich A.A. — data collection and analysis, draft manuscript preparation;
Minigalieva I.A. — study conception and design, draft manuscript preparation;
Sutunkova M.P. — study conception and design;
Butakova I.V. — data collection and analysis;
Bateneva V.A. — data collection and analysis;
Privalova L.I. — study conception and design, scientific editing.
All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

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: February 5, 2024 / Accepted: February 9, 2024 / Published: March 15, 2024

About the authors

Yuliya V. Ryabova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural Federal University named after the first President of Russia B.N. Yeltsin

Author for correspondence.
Email: ryabova@ymrc.ru
ORCID iD: 0000-0003-2677-0479

Researcher, head of the Laboratory of scientific foundations of bioprevention, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ryabova@ymrc.ru

Russian Federation

Lada V. Shabardina

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

Email: lada.shabardina@mail.ru
ORCID iD: 0000-0002-8284-0008

Laboratory assistant of the Department of toxicology and bioprevention Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: lada.shabardina@mail.ru

Russian Federation

Aleksandr A. Keskevich

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

Email: keskevichaa@ymrc.ru
ORCID iD: 0009-0008-4260-4626

Doctor of physical and rehabilitation medicine Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: keskevichaa@ymrc.ru

Russian Federation

Ilzira A. Minigalieva

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural Federal University named after the first President of Russia B.N. Yeltsin

Email: ilzira@ymrc.ru
ORCID iD: 0000-0002-1743-7642

MD, PhD, DSci., head of the Dept. of toxicology and bioprevention, Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ilzira@ymrc.ru

Russian Federation

Marina P. Sutunkova

Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers; Ural State Medical University

Email: sutunkova@ymrc.ru
ORCID iD: 0000-0002-1743-7642

MD, PhD, DSci., Director of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: sutunkova@ymrc.ru

Russian Federation

Inna V. Butakova

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

Email: butakovaiv@ymrc.ru
ORCID iD: 0000-0002-9871-9712

Junior researcher of the Clinics for the Therapy and Diagnostics of Occupational Diseases of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: butakovaiv@ymrc.ru

Russian Federation

Vlada A. Bateneva

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

Email: bateneva@ymrc.ru
ORCID iD: 0000-0002-4694-0175

Laboratory assistant of the Department of toxicology and bioprevention of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: bateneva@ymrc.ru

Russian Federation

Larisa I. Privalova

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

Email: privalovali@yahoo.com
ORCID iD: 0000-0002-1442-6737

MD, PhD, DSci., Sciences, Professor, chief researcher of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: privalovali@yahoo.com

Russian Federation

References

  1. Genchi G., Sinicropi M.S., Lauria G., Carocci A., Catalano A. The effects of cadmium toxicity. Int. J. Environ. Res. Public Health. 2020; 17(11): 3782. https://doi.org/10.3390/ijerph17113782
  2. Wang B., Du Y. Cadmium and its neurotoxic effects. Oxid. Med. Cell. Longev. 2013; 2013: 898034. https://doi.org/10.1155/2013/898034
  3. Karoui-Kharrat D., Kaddour H., Hamdi Y., Mokni M., Amri M., Mezghani S. Response of antioxidant enzymes to cadmium-induced cytotoxicity in rat cerebellar granule neurons. Open Life Sci. 2017; 12(1): 113–9. https://doi.org/10.1515/biol-2017-0013
  4. Branca J.J.V., Morucci G., Pacini A. Cadmium-induced neurotoxicity: still much ado. Neural Regen. Res. 2018; 13(11): 1879–82. https://doi.org/10.4103/1673-5374.239434
  5. Minigalieva I.A., Ryabova Yu.V., Sutunkova M.P., Gurvich V.B., Privalova L.I., Panov V.G., et al. The combined action of lead and physical load in a subchronic experiment on rats. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2021; 100(12): 1404–11. https://doi.org/10.47470/0016-9900-2021-100-12-1404-1411 https://elibrary.ru/sjnnkh (in Russian)
  6. Yang L., Wu C., Li Y., Dong Y., Wu C.Y., Lee R.H., et al. Long-term exercise pre-training attenuates Alzheimer’s disease-related pathology in a transgenic rat model of Alzheimer’s disease. Geroscience. 2022; 44(3): 1457–77. https://doi.org/10.1007/s11357-022-00534-2
  7. Carmichael M.D., Davis J.M., Murphy E.A., Brown A.S., Carson J.A., Mayer E., et al. Recovery of running performance following muscle-damaging exercise: relationship to brain IL-1beta. Brain Behav. Immun. 2005; 19(5): 445–52. https://doi.org/10.1016/j.bbi.2005.03.012
  8. Meeusen R., Watson P., Hasegawa H., Roelands B., Piacentini M.F. Central fatigue: the serotonin hypothesis and beyond. Sports Med. 2006; 36(10): 881–909. https://doi.org/10.2165/00007256-200636100-00006
  9. Khusainov D.R., Korenyuk I.I., Shakhmatova V.I., Tumanyants K.N., Tribrat N.S., Khorol’skaya K.D., et al. The peculiar features of cognitive processes in rats exposed to a hypomagnetic field using moderate magnetic shielding. Biofizika. 2020; 65(5): 876–82. https://doi.org/10.1134/S0006350920050097 https://elibrary.ru/jnjklo
  10. Wu C., Yang L., Li Y., Dong Y., Yang B., Tucker L.D., et al. Effects of exercise training on anxious-depressive-like behavior in Alzheimer rat. Med. Sci. Sports Exerc. 2020; 52(7): 1456–69. https://doi.org/10.1249/MSS.0000000000002294
  11. Lumley T., Diehr P., Emerson S., Chen L. The importance of the normality assumption in large public health data sets. Annu. Rev. Public Health. 2002; 23: 151–69. https://doi.org/10.1146/annurev.publhealth.23.100901.140546
  12. Leret M.L., Millán J.A., Antonio M.T. Perinatal exposure to lead and cadmium affects anxiety-like behaviour. Toxicology. 2003; 186(1–2): 125–30. https://doi.org/10.1016/s0300-483x(02)00728-x
  13. Gonçalves J.F., Nicoloso F.T., da Costa P., Farias J.G., Carvalho F.B., da Rosa M.M., et al. Behavior and brain enzymatic changes after long-term intoxication with cadmium salt or contaminated potatoes. Food Chem. Toxicol. 2012; 50(10): 3709–18. https://doi.org/10.1016/j.fct.2012.07.016
  14. Lamtai M., Chaibat J., Ouakki S., Berkiks I., Rifi E.H., El Hessni A., et al. Effect of chronic administration of cadmium on anxiety-like, depression-like and memory deficits in male and female rats: possible involvement of oxidative stress mechanism. J. Behav. Brain Sci. 2018; 8(5): 240–68. https://doi.org/10.4236/jbbs.2018.85016
  15. Taniguti E.H., Ferreira Y.S., Stupp I.J.V., Fraga-Junior E.B., Mendonça C.B., Rossi F.L., et al. Neuroprotective effect of melatonin against lipopolysaccharide-induced depressive-like behavior in mice. Physiol. Behav. 2018; 188: 270–5. https://doi.org/10.1016/j.physbeh.2018.02.034
  16. Singh P.K., Singh M.K., Yadav R.S., Nath R., Mehrotra A., Rawat A., et al. Omega-3 fatty acid attenuates oxidative stress in cerebral cortex, cerebellum, and hippocampus tissue and improves neurobehavioral activity in chronic lead-induced neurotoxicity. Nutr. Neurosci. 2019; 22(2): 83–97. https://doi.org/10.1080/1028415X.2017.1354542
  17. Model C.S., Gomes L.M., Scaini G., Ferreira G.K., Gonçalves C.L., Rezin G.T., et al. Omega-3 fatty acids alter behavioral and oxidative stress parameters in animals subjected to fenproporex administration. Metab. Brain Dis. 2014; 29(1): 185–92. https://doi.org/10.1007/s11011-013-9473-4
  18. Hirota K., Matsuoka M. N-acetylcysteine restores the cadmium toxicity of Caenorhabditis elegans. Biometals. 2021; 34(5): 1207–16. https://doi.org/10.1007/s10534-021-00322-z
  19. Morgan A.M., Hassanen E.I., Ogaly H.A., Al Dulmani S.A., Al-Zahrani F.A.M., Galal M.K., et al. The ameliorative effect of N-acetylcysteine against penconazole induced neurodegenerative and neuroinflammatory disorders in rats. J. Biochem. Mol. Toxicol. 2021; 35(10): e22884. https://doi.org/10.1002/jbt.22884
  20. Ragheb S.R., El Wakeel L.M., Nasr M.S., Sabri N.A. Impact of rutin and vitamin C combination on oxidative stress and glycemic control in patients with type 2 diabetes. Clin. Nutr. ESPEN. 2020; 35: 128–35. https://doi.org/10.1016/j.clnesp.2019.10.015
  21. Gonçalves J.F., Fiorenza A.M., Spanevello R.M., Mazzanti C.M., Bochi G.V., Antes F.G., et al. N-acetylcysteine prevents memory deficits, the decrease in acetylcholinesterase activity and oxidative stress in rats exposed to cadmium. Chem. Biol. Interact. 2010; 186(1): 53–60. https://doi.org/10.1016/j.cbi.2010.04.011
  22. Li X., Lv Y., Yu S., Zhao H., Yao L. The effect of cadmium on Aβ levels in APP/PS1 transgenic mice. Exp. Ther. Med. 2012; 4(1): 125–30. https://doi.org/10.3892/etm.2012.562
  23. Ambali S.F., Idris S.B., Onukak C., Shittu M., Ayo J.O. Ameliorative effects of vitamin C on short-term sensorimotor and cognitive changes induced by acute chlorpyrifos exposure in Wistar rats. Toxicol. Ind. Health. 2010; 26(9): 547–58. https://doi.org/10.1177/0748233710373086
  24. Moosavirad S.A., Rabbani M., Sharifzadeh M., Hosseini-Sharifabad A. Protective effect of vitamin C, vitamin B12 and omega-3 on lead-induced memory impairment in rat. Res. Pharm. Sci. 2016; 11(5): 390–6. https://doi.org/10.4103/1735-5362.192490
  25. Dixit S., Bernardo A., Walker J.M., Kennard J.A., Kim G.Y., Kessler E.S., et al. Vitamin C deficiency in the brain impairs cognition, increases amyloid accumulation and deposition, and oxidative stress in APP/PSEN1 and normally aging mice. ACS Chem. Neurosci. 2015; 6(4): 570–81. https://doi.org/10.1021/cn500308h
  26. da Costa M., Bernardi J., Costa L., Fiuza T., Brandão R., Ribeiro M.F., et al. N-acetylcysteine treatment attenuates the cognitive impairment and synaptic plasticity loss induced by streptozotocin. Chem. Biol. Interact. 2017; 272: 37–46. https://doi.org/10.1016/j.cbi.2017.05.008
  27. Kitamura Y., Ushio S., Sumiyoshi Y., Wada Y., Miyazaki I., Asanuma M., et al. N-acetylcysteine attenuates the anxiety-like behavior and spatial cognition impairment induced by doxorubicin and cyclophosphamide combination treatment in rats. Pharmacology. 2021; 106(5-6): 286–93. https://doi.org/10.1159/000512117
  28. Zysset-Burri D.C., Bellac C.L., Leib S.L., Wittwer M. Vitamin B6 reduces hippocampal apoptosis in experimental pneumococcal meningitis. BMC Infect. Dis. 2013; 13: 393. https://doi.org/10.1186/1471-2334-13-393
  29. Lisakovska O., Labudzynskyi D., Khomenko A., Isaev D., Savotchenko A., Kasatkina L., et al. Brain vitamin D3-auto/paracrine system in relation to structural, neurophysiological, and behavioral disturbances associated with glucocorticoid-induced neurotoxicity. Front. Cell. Neurosci. 2023; 17: 1133400. https://doi.org/10.3389/fncel.2023.1133400
  30. AlJohri R., AlOkail M., Haq S.H. Neuroprotective role of vitamin D in primary neuronal cortical culture. eNeurologicalSci. 2018; 14: 43–8. https://doi.org/10.1016/j.ensci.2018.12.004
  31. Razak M.A., Begum P.S., Viswanath B., Rajagopal S. Multifarious beneficial effect of nonessential amino acid, glycine: a review. Oxid. Med. Cell. Longev. 2017; 2017: 1716701. https://doi.org/10.1155/2017/1716701
  32. Torkova A.A., Lisitskaya K.V., Filimonov I.S., Glazunova O.A., Kachalova G.S., Golubev V.N., et al. Physicochemical and functional properties of Cucurbita maxima pumpkin pectin and commercial citrus and apple pectins: A comparative evaluation. PLoS One. 2018; 13(9): e0204261. https://doi.org/10.1371/journal.pone.0204261
  33. Méndez-Armenta M., Ríos C. Cadmium neurotoxicity. Environ. Toxicol. Pharmacol. 2007; 23(3): 350–8. https://doi.org/10.1016/j.etap.2006.11.009

Supplementary files

Supplementary Files
Action
1. JATS XML

Copyright (c) 2024 Ryabova Y.V., Shabardina L.V., Keskevich A.A., Minigalieva I.A., Sutunkova M.P., Butakova I.V., Bateneva V.A., Privalova L.I.



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.