Induction of apoptosis at the molecular genetic level exposed to lead oxide nanoparticles in a chronic animal experiment

Cover Page

Cite item

Full Text

Abstract

Introduction. Workers of industrial enterprises and the population living nearby are at risk of lead poisoning. Lead exposure can lead to irreversible negative consequences for the body, including hepatic and renal dysfunction, hematopoietic damage, cognitive dysfunction, and impairment of the genetic apparatus of the human cell. In this regard, it is necessary to study characteristics of the toxic effect of lead oxide nanoparticles (PbO NPs) to determine their health effects and minimize related disorders and diseases.

The purpose of the study was to determine the level of expression of the BAX, BCL-2, P53, GSTM1, GSTP1, and SOD2 genes in various organs of laboratory rats following the exposure to lead oxide nanoparticles.

Materials and methods. Twenty mature female albino Wistar rats were used in a four month experiment with chronic inhalation exposure to PbO NPs, 10 animals per group (exposure and control). The mean concentration of PbO NPs in the inhaled air was 0.215 mg/m3. At the end of the exposure period, organ fragments from the decapitated animals were fixed in liquid nitrogen and subsequently stored in a freezer at –80 °C. Total RNA was isolated from tissues using the ExtractRNA reagent. The expression level was determined by quantitative reverse transcription real-time PCR.

Results. The BAX expression in the liver of rats exposed to PbO NPs for 4 months was by 2.2 times higher than in the control group (p=0.009). We observed a trend towards an increase in the BAX/BCL-2 ratio in hepatocytes indicating apoptotic processes. The P53 expression level was by 1.4 times higher in the olfactory bulb of the exposed rats (p = 0.025) when compared to the controls. No changes were found in the expression levels of antioxidant genes GSTM1, GSTP1, and SOD2.

Limitations. The study was conducted using female Wistar rats with no potential sex differences taken into account.

Conclusion. Chronic inhalation exposure to PbO NPs induces apoptosis in rat liver through the BAX/BCL-2 pathway and rat brain through the regulation of P53.

Compliance with ethical standards. According to the Conclusion of the local Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers keeping, nutrition, care of animals and their removal from the experiment were carried out in accordance with generally accepted requirements, taking into account ARRIVE guidelines. The studies were approved by the Ethics Committee of the Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers (protocol No. 4 of July 12, 2022).

Contribution:
Bereza I.A. — data collection and processing, statistical analysis, draft manuscript preparation, editing;
Shaikhova D.R. — data collection and processing, draft manuscript preparation, editing;
Amromina A.M. — data collection and processing, draft manuscript preparation, editing;
Ryabova Yu.V. — data collection, editing;
Minigalieva I.A. — study conception and design, editing;
Sutunkova M.P. — study conception and design.
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: January 10, 2024 / Accepted: February 9, 2024 / Published: March 15, 2024

 

About the authors

Ivan A. Bereza

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

Author for correspondence.
Email: berezaia@ymrc.ru
ORCID iD: 0000-0002-4109-9268

Researcher, Department of Molecular Biology and Electron Microscopy, Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: berezaia@ymrc.ru

Russian Federation

Daria R. Shaikhova

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

Email: darya.boo@mail.ru
ORCID iD: 0000-0002-7029-3406

Researcher, Department of Molecular Biology and Electron Microscopy, Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: darya.boo@mail.ru

Russian Federation

Anna M. Amromina

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

Email: amrominaam@ymrc.ru
ORCID iD: 0000-0001-8794-7288

Junior Researcher, Department of Molecular Biology and Electron Microscopy, Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: amrominaam@ymrc.ru

Russian Federation

Yuliya V. Ryabova

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

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

MD, PhD, Head of Laboratory of Scientific Bases for Biological Prophylaxis, Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: ryabovayuvl@yandex.ru

Russian Federation

Ilzira A. Minigalieva

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

Email: ilzira-minigalieva@yandex.ru
ORCID iD: 0000-0002-0097-7845

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

e-mail: ilzira-minigalieva@yandex.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, Medical Research Center for Prophylaxis and Health Protection in Industrial Workers, Yekaterinburg, 620014, Russian Federation

e-mail: sutunkova@ymrc.ru

Russian Federation

References

  1. Baloch S., Kazi T.G., Baig J.A., Afridi H.I., Arain M.B. Occupational exposure of lead and cadmium on adolescent and adult workers of battery recycling and welding workshops: Adverse impact on health. Sci. Total Environ. 2020; 720: 137549. https://doi.org/10.1016/j.scitotenv.2020.137549
  2. Xiaobo L., Jin C., Yang J., Liu Q., Wu S., Li D., et al. Prenatal and lactational lead exposure enhanced oxidative stress and altered apoptosis status in offspring rats’ hippocampus. Biol. Trace Elem. Res. 2013; 151(1): 75–84. https://doi.org/10.1007/s12011-012-9531-5
  3. Singh N., Kumar A., Gupta V.K., Sharma B. Biochemical and molecular bases of lead-induced toxicity in mammalian systems and possible mitigations. Chem. Res. Toxicol. 2018; 31(10): 1009–21. https://doi.org/10.1021/acs.chemrestox.8b00193
  4. Peng J., Zhou F., Wang Y., Xu Y., Zhang H., Zou F., et al. Differential response to lead toxicity in rat primary microglia and astrocytes. Toxicol. Appl. Pharmacol. 2019; 363: 64–71. https://doi.org/10.1016/j.taap.2018.11.010
  5. Sutunkova M.P., Solovyeva S.N., Chernyshov I.N., Klinova S.V., Gurvich V.B., Shur V.Y., et al. Manifestation of systemic toxicity in rats after a short-time inhalation of lead oxide nanoparticles. Int. J. Mol. Sci. 2020; 21(3): 690. https://doi.org/10.3390/ijms21030690
  6. Charkiewicz A.E., Backstrand J.R. Lead toxicity and pollution in Poland. Int. J. Environ. Res. Public Health. 2020; 17(12): 4385. https://doi.org/10.3390/ijerph17124385
  7. Leber B., Geng F., Kale J., Andrews D.W. Drugs targeting Bcl-2 family members as an emerging strategy in cancer. Expert Rev. Mol. Med. 2010; 12: e28. https://doi.org/10.1017/S1462399410001572
  8. Navazani P., Vaseghi S., Hashemi M., Shafaati M.R., Nasehi M. Effects of treadmill exercise on the expression level of BAX, BAD, BCL-2, BCL-XL, TFAM, and PGC-1α in the hippocampus of thimerosal-treated rats. Neurotox. Res. 2021; 39(4): 1274–84. https://doi.org/10.1007/s12640-021-00370-w
  9. Lee I.C., Ko J.W., Park S.H., Shin N.R., Shin I.S., Moon C., et al. Comparative toxicity and biodistribution assessments in rats following subchronic oral exposure to copper nanoparticles and microparticles. Part. Fibre Toxicol. 2016; 13(1): 56. https://doi.org/10.1186/s12989-016-0169-x
  10. Adiguzel C., Karaboduk H., Apaydin F.G., Kalender S., Kalender Y. Comparison of nickel oxide nano and microparticles toxicity in rat liver: molecular, biochemical, and histopathological study. Toxicol. Res. (Camb.) 2023; 12(5): 741–50. https://doi.org/10.1093/toxres/tfad062
  11. Katsnelson B.A., Degtyareva T.D., Minigalieva I.А., Privalova L.I., Kuzmin S.V., Yeremenko O.S., et al. Sub-chronic systemic toxicity and bio-accumulation of Fe3O4 nano- and micro- particles following repeated intraperitoneal administration to rats. Int. J. Toxiсol. 2011; 30(1): 59–68. https://doi.org/10.1177/1091581810385149 https://elibrary.ru/ohtawh
  12. Amromina A.M., Shaikhova D.R., Bereza I.A., Tazhigulova A.V., Minigalieva I.A., Solov’eva S.N., et al. Some neurotoxic effects of lead nanoparticles on NMDA glutamate receptor gene expression and behavioral responses in Wistar rats. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2022; 101(12): 1581–7. https://doi.org/10.47470/0016-9900-2022-101-12-1581-1587 https://elibrary.ru/rcwafq (in Russian)
  13. Offor S.J., Herbert O.C.M., Orisakwe O.E. Lead induced hepato-renal damage in male albino rats and effects of activated charcoal. Front. Pharmacol. 2017; 8: 107. https://doi.org/10.3389/fphar.2017.00107
  14. Sutunkova M.P., Minigalieva I.A., Klinova S.V., Ryabova Yu.V., Tazhigulova A.V., Shabardina L.V., et al. Acute toxicity induced by inhalation exposure to lead oxide nanoparticles in rats. Zdorov’e naseleniya i sreda obitaniya – ZNiSO. 2023; 31(9): 24–30. https://doi.org/10.35627/2219-5238/2023-31-9-24-30 https://elibrary.ru/pmuwvc (in Russian)
  15. El-Tantawy W.H. Antioxidant effects of Spirulina supplement against lead acetate-induced hepatic injury in rats. J. Tradit. Complement. Med. 2016; 6(4): 327–31. https://doi.org/10.1016/j.jtcme.2015.02.001
  16. Galluzzi L., Pietrocola F., Bravo-San Pedro J.M., Amaravadi R.K., Baehrecke E.H., Cecconi F., et al. Autophagy in malignant transformation and cancer progression. EMBO J. 2015; 34(7): 856–80. https://doi.org/10.15252/embj.201490784
  17. Fadda L.M., Attia H.A., Al-Rasheed N.M., Ali H.M., Al-Rasheed N.M. Roles of some antioxidants in modulation of cardiac myopathy induced by sodium nitrite via down-regulation of mRNA expression of NF-κB, Bax, and Flt-1 and suppressing DNA damage. Saudi Pharm. J. 2018; 26(2): 217–23. https://doi.org/10.1016/j.jsps.2017.12.008
  18. Liu H., Chen C., Wang Q., Zhou C., Wang M., Li F., et al. The oxidative damage induced by lead sulfide nanoparticles in rat kidney. Mol. Cell. Toxicol. 2023; 19: 691–702. https://doi.org/10.1007/s13273-022-00296-0
  19. El-Shetry E.S., Mohamed A.A., Khater S.I., Metwally M.M.M., Nassan M.A., Shalaby S., et al. Synergistically enhanced apoptotic and oxidative DNA damaging pathways in the rat brain with lead and/or aluminum metals toxicity: expression pattern of genes OGG1 and P53. J. Trace Elem. Med. Biol. 2021; 68: 126860. https://doi.org/10.1016/j.jtemb.2021.126860
  20. Attafi I.M., Bakheet S.A., Korashy H.M. The role of NF-κB and AhR transcription factors in lead-induced lung toxicity in human lung cancer A549 cells. Toxicol. Mech. Methods. 2020; 30(3): 197–207. https://doi.org/10.1080/15376516.2019.1687629
  21. Hui Y., Liu C., Yang D., Zhang H., Xi Z. Comparative study of cytotoxicity, oxidative stress and genotoxicity induced by four typical nanomaterials: the role of particle size, shape and composition. J. Appl. Toxicol. 2009; 29(1): 69–78. https://doi.org/10.1002/jat.1385
  22. Feng X., Chen A., Zhang Y., Wang J., Shao L., Wei L. Central nervous system toxicity of metallic nanoparticles. Int. J. Nanomedicine. 2015; 10(1): 4321–40. https://doi.org/10.2147/IJN.S78308
  23. Bin S., Zhang Y., Liu J., Feng X., Zhou T., Shao L. Is neurotoxicity of metallic nanoparticles the cascades of oxidative stress? Nanoscale Res. Lett. 2016; 11(1): 291. https://doi.org/10.1186/s11671-016-1508-4

Supplementary files

Supplementary Files
Action
1. JATS XML
Download

Copyright (c) 2024 Bereza I.A., Shaikhova D.R., Amromina A.M., Ryabova Y.V., Minigalieva I.A., Sutunkova M.P.


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.