Comparative analysis of some long-term neurotoxic effects of lead acetate in adult rats and their offspring and the impact of bioprophylaxis

Introduction. Some heavy metals, such as lead and its compounds, can cause health problems not only in the exposed individuals but also in subsequent generations. Research on the development and experimental testing of bioprophylactic complexes containing components with protective properties has demonstrated high efficacy. It remains unclear, however, whether measures of biological prophylaxis cannot only enhance the resistance of individuals exposed to lead but also mitigate long-term consequences of this exposure in their offspring.

The aim of this study was to evaluate the efficacy of bioprophylaxis of late neurotoxic effects of subchronic exposure to lead acetate in adult rats and their offspring.

Materials and methods. Lead acetate was administered orally to 4-month-old albino rats of both sexes for 45 days in the dose of 85,6 mg/kg b.w. Some animals also received a bioprophylactic complex (BPC) containing pectin, multivitamin and mineral supplements, amino acids (glutamic acid, glycine, and cysteine), iodine, iron, and calcium supplements, and fish oil rich with omega-3 fatty acids. We equally divided ninety six adult rats (F0) into four groups: the control group, the lead acetate exposure group, the group exposed to lead acetate and receiving the BPC, and the group administered the BPC only. After breastfeeding cessation, 96 pups (F1) were randomly selected from the total number of newborn rats to evaluate long-term toxic effects of lead and BPC efficacy.

Results. We observed a decrease in lead concentrations in the mammary glands of the F0 rats receiving BPC. Pathological behavioral changes were detected in the offspring of the exposed rats despite the absence of direct exposure. The components of the protective complex reduced the severity of the late neurotoxic effects of lead in F1 rats.

Limitations. Rats were neither exposed to lead acetate nor administered the bioprophylactic complex during mating, pregnancy, and lactation periods. Sex-specific toxic effects in the parents and offspring were not assessed either.

Conclusion. Our findings are the first to demonstrate the ability of bioprophylactic measures to not only increase resistance but also reduce the severity of long-term neurotoxic effects. These properties of bioprophylaxis open new opportunities for managing human health risks and reducing the burden of environmental diseases and disorders in future generations.

Compliance with ethical standards. The study was approved by the local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol of February 3, 2025).

Contributions:
Sutunkova M.P. — study design, editing;
Nikogosyan K.M. — data collection and processing, draft manuscript preparation, editing;
Bateneva V.A. — data analysis, editing;
Minigalieva I.A. — study conception, editing;
Shtin T.N. — data collection.
All authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Conflict of interest. The authors declare no conflict of interest.

Funding. The study had no sponsorship.

Received: March 3, 2026 / Revised: April 24, 2026 / Accepted: May 20, 2026 / Published: June 18, 2026

1. Santa Maria M.P., Hill B.D., Kline J. Lead (Pb) neurotoxicology and cognition. Appl. Neuropsychol. Child. 2018; 8(3): 272–93. https://doi.org/10.1080/21622965.2018.1428803

2. Ramírez Ortega D., González Esquivel D.F., Blanco Ayala T., Pineda B., Gómez Manzo S., Marcial Quino J., et al. Cognitive impairment induced by lead exposure during lifespan: mechanisms of lead neurotoxicity. Toxics. 2021; 9(2): 23. https://doi.org/10.3390/toxics9020023

3. Ryabova Yu.V., Kungurtseva A.K., Petrunina E.M., Nikogosyan K.M., Klinova S.V., Minigalieva I.A., et al. Changes in health effects of lead exposure caused by exercise and the impact of biological prophylaxis on rats’ central nervous system. Meditsina truda i ekologiya cheloveka. 2024; (2): 191–210. https://doi.org/10.24412/2411-3794-2024-10213 https://elibrary.ru/swxmma (in Russian)

4. Minigalieva I.A., Nikogosyan K.M., Sutunkova M.P., Kungurtseva A.K., Petrunina E.M., Bateneva V.A. Experimental evaluation of a bioprophylactic complex aimed at increasing resistance to neurotoxic effects of lead oxide nanoparticles. Toksikologicheskii vestnik. 2025; 33(2): 86–92. https://doi.org/10.47470/0869-7922-2025-33-2-86-92 https://elibrary.ru/bgxhph (in Russian)

5. Wang R., Liang R., Dai T., Chen J., Shuai X., Liu C. Pectin-based adsorbents for heavy metal ions: a review. Trends Food Sci. Technol. 2019; 91: 319–29. https://doi.org/10.1016/j.tifs.2019.07.033

6. Lopes A.C., Peixe T.S., Mesas A.E., Paoliello M.M. Lead exposure and oxidative stress: a systematic review. Rev. Environ. Contam. Toxicol. 2016; 236: 193–238. https://doi.org/10.1007/978-3-319-20013-2_3

7. Fedoriv O.Ye., Kopach A.Ye., Melnyk N.A. Impact of lead acetate and sodium and potassium stearates on lipid peroxidation processes in the body of experimental animals. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2021; 100(4): 406–10. https://doi.org/10.47470/0016-9900-2021-100-4-406-410 https://elibrary.ru/ontqas (in Russian)

8. Njus D., Kelley P.M., Tu Y.J., Schlegel H.B. Ascorbic acid: the chemistry underlying its antioxidant properties. Free Radic. Biol. Med. 2020; 159: 37–43. https://doi.org/10.1016/j.freeradbiomed.2020.07.013

9. Santos K.L., Bragança V.A., Pacheco L.V., Ota S.S., Aguiar C.P., Borges R.S. Essential features for antioxidant capacity of ascorbic acid (vitamin C). J. Mol. Model. 2022; 28(1): 1. https://doi.org/10.1007/s00894-021-04994-9

10. Palace V.P., Khaper N., Qin Q., Singal P.K. Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radic. Biol. Med. 1999; 26(5–6): 746–61. https://doi.org/10.1016/s0891-5849(98)00266-4

11. Galli F., Azzi A., Birringer M., Cook-Mills J.M., Eggersdorfer M., Frank J., et al. Vitamin E: emerging aspects and new directions. Free Radic. Biol. Med. 2017; 102: 16–36. https://doi.org/10.1016/j.freeradbiomed.2016.09.017

12. Florea A.M., Taban J., Varghese E., Alost B.T., Moreno S., Büsselberg D. Lead (Pb²+) neurotoxicity: ion mimicry with calcium (Ca²+) impairs synaptic transmission. Review with animated illustrations of the pre- and post-synaptic effects of lead. J. Local Glob. Health Sci. 2013; 2013(1): 4. https://doi.org/10.5339/jlghs.2013.4

13. Virgolini M.B., Aschner M. Molecular mechanisms of lead neurotoxicity. Adv. Neurotoxicol. 2021; 5: 159–213. https://doi.org/10.1016/bs.ant.2020.11.002

14. Tyrtyshnaya A.A. Mechanisms of docosahexaenoic acid influence on cognitive functions at neuroinflammation. Izvestiya Samarskogo nauchnogo tsentra Rossiiskoi akademii nauk. 2014; 16(5–2): 809–12. https://elibrary.ru/tnyyat (in Russian)

15. Manzhulo I.V., Tyrtyshnaia A.A., Manzhulo O.S., Starinets A.A., Kasyanov S.P., Dyuizen I.V. Neuroprotective activity of docosahexaenoic acid in the central and peripheral nervous system after chronic constriction injury of the sciatic nerve. Neurochem. J. 2020; 14(1): 101–7. https://doi.org/10.1134/s1819712420010158 https://elibrary.ru/vbobly

16. Averill-Bates D.A. The antioxidant glutathione. Vitam. Horm. 2023; 121: 109–41. https://doi.org/10.1016/bs.vh.2022.09.002

17. Fossati M., Charrier C. Trans-synaptic interactions of ionotropic glutamate receptors. Curr. Opin. Neurobiol. 2021; 66: 85–92. https://doi.org/10.1016/j.conb.2020.09.001

18. Niciu M.J., Kelmendi B., Sanacora G. Overview of glutamatergic neurotransmission in the nervous system. Pharmacol. Biochem. Behav. 2012; 100(4): 656–64. https://doi.org/10.1016/j.pbb.2011.08.008

19. Dupuis J.P., Nicole O., Groc L. NMDA receptor functions in health and disease: Old actor, new dimensions. Neuron. 2023; 111(15): 2312–28. https://doi.org/10.1016/j.neuron.2023.05.002

20. Morris R.G. NMDA receptors and memory encoding. Neuropharmacology. 2013; 74: 32–40. https://doi.org/10.1016/j.neuropharm.2013.04.014

21. Hanada T. Ionotropic glutamate receptors in epilepsy: A review focusing on AMPA and NMDA receptors. Biomolecules. 2020; 10(3): 464. https://doi.org/10.3390/biom10030464

22. Zhang Y., Li P., Feng J., Wu M. Dysfunction of NMDA receptors in Alzheimer’s disease. Neurol. Sci. 2016; 37(7): 1039–47. https://doi.org/10.1007/s10072-016-2546-5

23. Wang R., Reddy P.H. Role of glutamate and NMDA receptors in Alzheimer’s disease. J. Alzheimers Dis. 2017; 57(4): 1041–8. https://doi.org/10.3233/JAD-160763

24. Hansen K.B., Yi F., Perszyk R.E., Menniti F.S., Traynelis S.F. NMDA receptors in the central nervous system. Methods Mol. Biol. 2017; 1677: 1–80. https://doi.org/10.1007/978-1-4939-7321-7_1