Transcriptional activity of Gstp and Gclc genes under prolonged acrylamide exposure

Introduction. Acrylamide is a toxicant encountered in both industrial and domestic settings. It forms during the thermal processing of food and is used in industrial processes, increasing the risk of human exposure. Acrylamide has nephrotoxic, neurotoxic, and genotoxic properties, but its impact on cellular mechanisms, including antioxidant and detoxification systems, remains insufficiently studied. Investigating the expression of the Gstp and Gclc genes, involved in antioxidant defense, is crucial for understanding the pathogenesis of acrylamide-induced changes.Th

The aim of the work was to study the changes in the expression of the Gstp and Gclc genes under prolonged acrylamide exposure and to evaluate the effectiveness of preventive measures using oxymethyluracil-based compounds.

Materials and methods. The experiment involved sixty male white rats received acrylamide (5 mg/kg body weight) daily for 90 days. Preventive correction was conducted one hour before acrylamide administration. Gene expression levels were assessed using real-time PCR.

Results. Prolonged acrylamide exposure caused changes in the expression of the Gstp and Gclc genes in kidney tissue. The expression of Gstp significantly increased, especially in groups received preventive correction with ascorbic acid-containing compounds. The expression of Gclc initially decreased but increased after 3 months, particularly with the use of acetylcysteine and sodium succinate.

Limitations. This study focused on evaluating the expression levels of two key Gstp and Gclc genes, associated with antioxidant defense under prolonged acrylamide exposure. However, to gain a more comprehensive understanding of the pathogenic mechanisms of acrylamide-induced nephrotoxicity, further analysis is required to include other genetic markers related to detoxification, inflammation, and oxidative stress. There is also needed the multifactorial approach, incorporating the assessment of biochemical and physiological indicators of toxic exposure.

Conclusion. Acrylamide negatively affects kidney function, as evidenced by changes in the expression of Gstp and Gclc genes. The most effective prevention was observed with the use of oxymethyluracil combined with acetylcysteine.

Compliance with ethical standards. The study was approved by the Bioethics Committee of the Ufa Research Institute of Occupational Health and Human Ecology (protocol of the meeting dated December 17, 2024, No. 01-12). Experiments were conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123) and Directive 2010/63/EU of the European Parliament and of the Council of September 22, 2010, on the protection of animals used for scientific purposes.

Contributions:
Yakupova T.G. – study concept and design, material collection and processing, statistical analysis, writing text;
Karimov D.D., Karimov D.O. – study concept and design, statistical analysis;
Ryabova Yu.V., Repina E.F., Garipova Z.R. – material collection and processing;
Mukhamadieva G.F. – 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. This study was conducted as part of the implementation of the state assignment included in the sectoral research program of Rospotrebnadzor, titled «Development of scientific foundations for the national system ensuring sanitary and epidemiological well-being, health risk management, and improving the quality of life of the population of the Russian Federation» for the period 2021–2025, item 6.1.8. State registration number: 121062100058-8.

Received: January 19 , 2025 / Revised: January 31, 2025 / Accepted: March 26, 2025 / Published: July 31, 2025

1. Rice J.M. The carcinogenicity of acrylamide. Mutat. Res. 2005; 7(580): 3–20. https://doi.org/10.1016/j.mrgentox.2004.09.008

2. Erdemli M.E., Aksungur Z., Gul M., Yigitcan B., Bag H.G., Altinoz E., et al. The effects of acrylamide and vitamin E on kidneys in pregnancy: an experimental study. J. Matern. Fetal. Neonatal. Med. 2019; 32(22): 3747–56. https://doi.org/10.1080/14767058.2018.1471675

3. Mazhar F.M., Moawad K.M., El-Dakdoky M.H., Amer A.S. Fetotoxicity of 2,4-dichlorophenoxyacetic acid in rats and the protective role of vitamin E. Toxicol. Ind. Health. 2014; 30(5): 480–8. https://doi.org/10.1177/0748233712459915

4. Yerlikaya F.H., Yener Y. The dietary acrylamide intake adversely affects the serum trace element status. Biol. Trace Elem. Res. 2013; 152(1): 75–81. https://doi.org/10.1007/s12011-013-9598-7

5. Jia Z., Liu M., Qu Z., Zhang Y., Yin S., Shan A. Toxic effects of zearalenone on oxidative stress, inflammatory cytokines, biochemical and pathological changes induced by this toxin in the kidney of pregnant rats. Environ. Toxicol. Pharmacol. 2014; 37(2): 580–91. https://doi.org/10.1016/j.etap.2014.01.010

6. Li L., Wang Z., Li Y., Ma F., Wang X., Yan H., et al. Allicin alleviates mitochondrial dysfunction in acrylamide-induced rat kidney involving the regulation of SIRT1. J. Agric. Food Chem. 2023; 71(42): 15785–95. https://doi.org/10.1021/acs.jafc.3c04687

7. Stadler R.H., Gökmen V. Acrylamide formation mechanisms. In: Acrylamide in Food. Volume 2. Academic Press; 2024: 1–17. https://doi.org/10.1016/B978-0-323-99119-3.00017-5

8. Virk-Baker M.K., Nagy T.R., Barnes S., Groopman J. Dietary acrylamide and human cancer: a systematic review of literature. Nutr. Cancer. 2014; 66: 774–90. https://doi.org/10.1080/01635581.2014.916323

9. Ibrahim D.S. Effect of vinpocetine against acrylamide-induced nephrotoxicity in rats. J. Biochem. Mol. Toxicol. 2024; 38(2): e23658. https://doi.org/10.1002/jbt.23658

10. Zhuchkova E.D., Shchepochkina O.Yu., Tereshkina O.I., Petrykina E.A. The medical use and standardization of antioxidants: medicines and excipients. Farmatsiya. 2015; (1): 48–52. https://elibrary.ru/tluiqp (in Russian)

11. Semla M., Goc Z., Martiniaková M., Omelka R., Formicki G. Acrylamide: a common food toxin related to physiological functions and health. Physiol. Res. 2017; 66(2): 205–17. https://doi.org/10.33549/physiolres.933381

12. Borisov V.V. Oxidative stress, antioxidants, and reproductive problems during the pandemic (clinical lecture). Klinicheskii razbor v obshchei meditsine. 2021; (3): 67–74. https://doi.org/10.47407/kr2021.2.3.00053 https://elibrary.ru/nfwbdm (in Russian)

13. Rifai L., Saleh F.A. A Review on acrylamide in food: occurrence, toxicity, and mitigation strategies. Int. J. Toxicol. 2020; 39(2): 93–102. https://doi.org/10.1177/1091581820902405

14. Matoso V., Bargi-Souza P., Ivanski F., Romano M.A., Romano R.M. Acrylamide: A review about its toxic effects in the light of Developmental Origin of Health and Disease (DOHaD) concept. Food Chem. 2019; 283: 422–30. https://doi.org/10.1016/j.foodchem.2019.01.054

15. Sengul E., Gelen V., Yildirim S., Tekin S., Dag Y. The effects of selenium in acrylamide-induced nephrotoxicity in rats: roles of oxidative stress, inflammation, apoptosis, and DNA damage. Biol. Trace Elem. Res. 2021; 199(1): 173–84. https://doi.org/10.1007/s12011-020-02111-0

16. Bedir F., Kocatürk H., Yapanoğlu T., Gürsul C., Arslan R., Mammadov R., et al. Protective effect of taxifolin against prooxidant and proinflammatory kidney damage associated with acrylamide in rats. Biomed. Pharmacother. 2021; 139: 111660. https://doi.org/10.1016/j.biopha.2021.111660

17. Kandemir F.M., Yıldırım S., Kucukler S., Caglayan C., Darendelioğlu E., Dortbudak M.B. Protective effects of morin against acrylamide-induced hepatotoxicity and nephrotoxicity: A multi-biomarker approach. Food Chem. Toxicol. 2020; 138: 111190. https://doi.org/10.1016/j.fct.2020.111190

18. Tüfekci K.K., Tatar M. Oleuropein mitigates acrylamide-induced nephrotoxicity by affecting placental growth factor immunoactivity in the rat kidney. Eurasian J. Med. 2023; 55(3): 228–33. https://doi.org/10.5152/eurasianjmed.2023.23043

19. Chesnokova N.P., Ponukalina E.V., Bizenkova M.N. General characteristic of the sources of the free radical formation and antioxidant systems. Uspekhi sovremennogo estestvoznaniya. 2006; (7): 37–41. https://elibrary.ru/ijitxh (in Russian)

20. Ali A., Ibrahim R., Ahmed A.F., Talaat E. Histological study of toxic effects of acrylamide on the liver and kidney of adult male albino rats. Minia J. Med. Res. 2020; 31(3): 345–50. https://doi.org/10.21608/mjmr.2022.220316

21. El Fakahany G.A., Nassar S.A., Elballat S.E. Alterations in Kidney of albino rat due to acrylamide exposure and the possible protective role of l-arginine (biochemical, histological, immunohistochemical and molecular study). Sys. Rev. Pharm. 2021; 12(3): 744–52.

22. Nasralla M.M., Zaki S.M., Attia R.A. Protective effect of resveratrol on acrylamide-induced renal impairment. Folia Morphol. (Warsz). 2021; 80(4): 985–93. https://doi.org/10.5603/FM.a2020.0133

23. Repina E.F., Karimov D.O., Baygildin S.S., Yakupova T.G., Khusnutdinova N.Yu., Shaikhlislamova E.R., et al. Evaluation of apoptosis gene expression and morphological changes in kidney tissue under acrylamide exposure and prophylactic drug correction. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2025; 104(1): 96–100. https://doi.org/10.47470/0016-9900-2025-104-1-96-100 https://elibrary.ru/pvwctq (in Russian)

24. Uthra C., Reshi M.S., Jaswal A., Yadav D., Shrivastava S., Sinha N., et al. Protective efficacy of rutin against acrylamide-induced oxidative stress, biochemical alterations and histopathological lesions in rats. Toxicol. Res. (Camb). 2022; 11(1): 215–25. https://doi.org/10.1093/toxres/tfab125

25. Mucci L.A., Lindblad P., Steineck G., Adami H.O. Dietary acrylamide and risk of renal cell cancer. Int. J. Cancer. 2004; 109(5): 774–6. https://doi.org/10.1002/ijc.20011