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Changes in the morphofunctional state of the liver under the influence of acrylamide and upon correction with complex compounds of oxymethyluracil in dynamics

https://doi.org/10.47470/0869-7922-2025-33-6-417-425

EDN: npqehr

Abstract

Introduction. Acrylamide is widely used in various industries and is recognized as a toxic compound. Considering the potential risks of its entry into the human body, further research is required to understand the mechanisms of its toxicity and to develop effective approaches for correcting pathological conditions caused by its exposure.

The purpose of the study was to evaluate changes in the morphofunctional state of the liver under the influence of acrylamide and correction with oxymethyluracil complexes in dynamics, based on biochemical, genetic and morphological parameters.

Material and methods. The experimental study was conducted on outbred male rats, which were administered acrylamide intragastrically at a dose of 5 mg/kg body weight over three months. Preventive correction was performed using oxymethyluracil complexes. Biochemical, genetic, and morphological studies were performed.

Results. The studies revealed that after 1.5 and 3 months, the activity of hepatic enzymes significantly increased, and minor changes were observed in the liver parenchyma. The expression of glutathione system genes decreased mid-experiment and increased by the end. Oxymethyluracil complexes demonstrated a certain hepatoprotective effect.

Limitations. For a deeper study of this problem, it is necessary to consider the effect of different dosages of the hepatotoxicant and the protective effectiveness of compounds in other modes of exposure to the body.

Conclusion. Long-term exposure to acrylamide at a dose of 5 mg/kg body weight had a hepatotoxic effect, manifested by increased activity of cytolysis marker enzymes, bidirectional changes in the expression of genes involved in detoxification processes depending on exposure duration, and, to a lesser extent, histological changes in organ structure. Complex compounds of oxymethyluracil exhibited hepatoprotective effects, with their corrective efficiency ranked as follows: MG-10 > MG-2 > MG-1.

Compliance with ethical standards. The study was approved by the Bioethical Commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (Protocol No. 01-10 dated 09.10.2024).

Authors’ contribution:
Khusnutdinova N.Yu. – conducting research, collecting and processing material, writing text;
Ryabova Yu.V. – material processing, text writing; editing;
Yakupova T.G. – conducting research, data collection and processing, statistical analysis;
Karimov D.O. – research concept and design, editing;
Smolyankin D.A., Akhmadeev A.R., Khmel A.O. – data collection and processing, statistical analysis;
Repina E.F. – data collection and processing, editing.
All co-authors – approval of the final version of the article, responsibility for the integrity of all parts of the article.

Acknowledgments. The authors express their gratitude to Alfiya Raisovna Gimadieva A.R., Candidate of Chemical Sciences, Senior Researcher at the Laboratory of Pharmacophore Cyclic Systems of the Ufa Institute of Chemistry, Ufa Federal Research Center of the Russian Academy of Sciences, for the development and synthesis of oxymethyluracil complexes.

Conflict of interests. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The work was carried out as part of the state assignment for the industry research program of Rospotrebnadzor “Scientific substantiation of the national system for ensuring sanitary and epidemiological welfare, managing health risks and improving the quality of life of the population of Russia” for 2021-2025, (clause 6.1.8), state registration number 121062100058-8. The synthesis of complex compounds of oxymethyluracil was carried out in accordance with the research plan of the Ufa Institute of Chemistry of the Ufa Federal Research Center of the Russian Academy of Sciences (State Registration Number AAAA-A19-119011790021-4).

Received: May 24, 2025 / Revised: June 22, 2025 / Accepted: November 25, 2025 / Published: January 15, 202

About the Authors

Nadezhda Yu. Khusnutdinova
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Researcher, Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: h-n-yu@yandex.ru



Yuliya V. Ryabova
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Candidate of Medical Sciences, Head of the Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: ryabovaiuvl@gmail.com



Tatyana G. Yakupova
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Junior Researcher, Laboratory of Genetics, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: tanya.kutlina.92@mail.ru



Denis O. Karimov
Ufa Research Institute of Occupational Medicine and Human Ecology; N.A. Semashko National Research Institute of Public Health
Россия

Candidate of Medical Sciences, Head of the Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: karimovdo@gmail.com



Denis A. Smolyankin
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Researcher, Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: smolyankin.denis@yandex.ru



Aidar R. Akhmadeev
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Junior Researcher, Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: dgaar87@gmail.com



Aleksandra O. Khmel
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Junior Researcher, Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: Khmel.al01@gmail.com



Elvira F. Repina
Ufa Research Institute of Occupational Medicine and Human Ecology
Россия

Candidate of Medical Sciences, Senior Researcher, Laboratory of Toxicology, Department of Toxicology and Genetics with the Experimental Laboratory Animal Clinic, Ufa Research Institute of Occupational Health and Human Ecology, Ufa, 450106, Russian Federation

e-mail: e.f.repina@bk.ru



References

1. Moorman W.J., Reutman S.S., Shaw P.B., Blade L.M., Marlow D., Vespe H., et аl. Occupational exposure to acrylamide in closed system production plants: Air levels and biomonitoring. J. Toxicol. Environ. Health A. 2012; 75(2): 100–11. https://doi.org/10.1080/15287394.2011.615109

2. Gökmen V., Palazoğlu T.K. Acrylamide formation in foods during thermal processing with a focus on frying. Food Bioprocess Technol. 2008; 1: 35-42. https://doi.org/10.1007/s11947-007-0005-2

3. Smith C.J., Perfetti T.A., Rumple M.A., Rodgman A., Doolittle D.J. "IARC group 2A Carcinogens" reported in cigarette mainstream smoke. Food Chem. Toxicol. 2000; 38(4): 371–83. https://doi.org/10.1016/s0278-6915(99)00156-8

4. Mousavi Khaneghah A., Fakhri Y., Nematollahi A., Seilani F., Vasseghian Y. The concentration of acrylamide in different food products: a global systematic review, meta-analysis, and meta-regression. Food Rev. Int. 2022; 38(6): 1286–304. https://doi.org/10.1080/87559129.2020.1791175

5. Kocadağlı T., Gökmen V. Formation of acrylamide in coffee. Curr. Opin. Food Sci. 2022; 45: 100842. https://doi.org/10.1016/j.cofs.2022.100842

6. 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

7. Exon J.H. A review of the toxicology of acrylamide. J. Toxicol. Environ. Health B Crit. Rev. 2006; 9(5): 397–412. https://doi.org/10.1080/10937400600681430

8. WHO. International agency for research on cancer. In: IARC Monographs on the Evaluation of Carcinogenic Risks to Man. Volume 60. Lyon; 1994: 1–560.

9. Johnson K.A., Gorzinski S.J., Bodner K.M., Campbell R.A., Wolf C.H., Friedman M.A., et al. Chronic toxicity and oncogenicity study on acrylamide incorporated in the drinking water of Fischer 344 rats. Toxicol. Appl. Pharmacol. 1986; 85(2): 154–68. https://doi.org/10.1016/0041-008x(86)90109-2

10. Hamdy S., Bakeer H., Eskander E., Sayed O.N. Effect of acrylamide on some hormones and endocrine tissues in male rats. Hum. Exp. Toxicol. 2012; 31(5): 483–91. https://doi.org/10.1177/0960327111417267

11. Sayed S., Alotaibi S.S., El-Shehawi A.M., Hassan M.M., Shukry M., Alkafafy M., et al. The Anti-Inflammatory, anti-apoptotic and antioxidant effects of a pomegranate-peel extract against acrylamide-induced hepatotoxicity in rats. Life (Basel). 2022; 12(2): 224. https://doi.org/10.3390/life12020224

12. Michalak J., Czarnowska-Kujawska M., Klepacka J., Gujska E. Effect of microwave heating on the acrylamide formation in foods. Molecules. 2020; 25(18): 4140. https://doi.org/10.3390/molecules25184140

13. Panel E.C. Scientific opinion on acrylamide in food. EFSA J. 2015; 13(6): 4104.

14. Pelucchi C., Bosetti C., Galeone C., La Vecchia C. Dietary acrylamide and cancer risk: an updated meta-analysis. Int. J. Cancer. 2015; 136(12): 2912–22. https://doi.org/10.1002/ijc.29339

15. Gu X., Manautou J.E. Molecular mechanisms underlying chemical liver injury. Expert Rev. Mol. Med. 2012; 14: e4. https://doi.org/10.1017/s1462399411002110

16. Mushkin V.A., Bakirov A.B., Repina E.F., Timasheva G.V., Khusnutdinova N.Yu., Smolyankin D.A. Study the effectiveness of oxymethyluracil as a means hepatoprotective. Meditsina truda i ekologiya cheloveka. 2015; (2): 55–60. https://elibrary.ru/txzdzj (in Russian).

17. EC. Directive 2010/63/EU of the European Parliament and of the Council of 22 September 2010 on the protection of animals used for scientific purposes. Off. J. Eur. Union. 2010; 276: 33–79.

18. Repina E.F., Gimadieva A.R., Myshkin V.A., Bakirov A.B., Timasheva G.V., Khusnutdinova N.Yu., et al. Anti-hypoxic activity of the new complex compound of oxymethyluracil with sodium succinate. Toksikologicheskii vestnik. 2017; (2): 40–2. https://doi.org/10.36946/0869-7922-2017-2-40-42 https://elibrary.ru/yrmnxp (in Russian)

19. Repina E.F., Myshkin V.A., Karimov D.O., Timasheva G.V., Khusnutdinova N.Yu., Smolyankin D.A., et al. Anti-hypoxic activity of the complex compound of oxymethyluracil with ascorbic acid. Toksikologicheskii vestnik. 2018; (4): 20–3. https://doi.org/10.36946/0869-7922-2018-4-20-23 https://elibrary.ru/xygvqt (in Russian)

20. Repina E.F., Bakirov A.B., Gimadieva A.R., Karimov D.O., Kudoyarov E.R., Timasheva G.V., et al. The assessment of the antihypoxic properties of the complex compound of oxymethyluracil with acetylcysteine in the model of histotoxic hypoxia. Gigiena i Sanitaria (Hygiene and Sanitation, Russian journal). 2022; 101(9): 1098–102. https://doi.org/10.47470/0016-9900-2022-101-9-1098-1102 https://elibrary.ru/zkhvyc (in Russian)

21. Dasari S., Ganjayi M.S., Meriga B. Glutathione S-transferase is a good biomarker in acrylamide induced neurotoxicity and genotoxicity. Interdiscip. Toxicol. 2018; 11(2): 115–21. https://doi.org/10.2478/intox-2018-0007

22. Zhang L., Zhang H., Miao Y., Wu S., Ye H., Yuan Y. Protective effect of allicin against acrylamide-induced hepatocyte damage in vitro and in vivo. Food Chem. Toxicol. 2012; 50(9): 3306–12. https://doi.org/10.1016/j.fct.2012.05.060

23. Glinghammar B., Rafter I., Lindström A.K., Hedberg J.J., Andersson H.B., Lindblom P., et al. Detection of the mitochondrial and catalytically active alanine aminotransferase in human tissues and plasma. Int. J. Mol. Med. 2009; 23(5): 621–31. https://doi.org/10.3892/ijmm_00000173

24. Green R.M., Flamm S. AGA technical review on the evaluation of liver chemistry tests. Gastroenterology. 2002; 123(4): 1367–84. https://doi.org/10.1053/gast.2002.36061

25. Gęgotek A., Skrzydlewska E. Ascorbic acid as antioxidant. Vitam. Horm. 2023; 121: 247–70. https://doi.org/10.1016/bs.vh.2022.10.008

26. Orlov Yu.P., Butrov A.V., Sviridov S.V., Afanasiev V.V., Kondratiyev A.N., Tsentsiper L.M., et al. Succinate and succinate dehydrogenase as a “foothold” in the Krebs cycle in critical conditions. Antibiotiki i khimioterapiya. 2023; 68(1-2): 57–68. https://doi.org/10.37489/0235-2990-2023-68-1-2-57-68 https://elibrary.ru/ywnubc (in Russian)

27. Chaudhary P., Janmeda P., Docea A.O., Yeskaliyeva B., Abdull Razis A.F., Modu B., et al. Oxidative stress, free radicals and antioxidants: potential crosstalk in the pathophysiology of human diseases. Front. Chem. 2023; 11: 1158198. https://doi.org/10.3389/fchem.2023.1158198

28. Bakirov A.B., Myshkin V.A., Repina E.F., Karimov D.O., Gimadiyeva A.R., Timasheva G.V., et al. Overcoming the hepatotoxicity of persistent organic pollutants: the role of pyrimidine antioxidants. Gigiena truda i meditsinskaya ekologiya. 2016; (3): 3–18. https://elibrary.ru/yptdfl (in Russian)

29. Aldini G., Altomare A., Baron G., Vistoli G., Carini M., Borsani L., et al. N-Acetylcysteine as an antioxidant and disulphide breaking agent: the reasons why. Free Radic. Res. 2018; 52(7): 751–62. https://doi.org/10.1080/10715762.2018.1468564

30. Kerksick C., Willoughby D. The antioxidant role of glutathione and N-Acetyl-Cysteine Supplements and exercise-induced oxidative stress. J. Int. Soc. Sports Nutr. 2005; 2(2): 38–44. https://doi.org/10.1186/1550-2783-2-2-38

31. Myshkin V.A., Enikeyev D.A., Srubilin D.V., Gimadieva A.R. Experimental evaluation of pyrimidine derivatives in models of toxic liver damage: a review. Nauchnoe obozrenie. Meditsinskie nauki. 2016; (3): 88–98. https://elibrary.ru/wlxigj (in Russian)

32. Wright D.J., Renoir T., Smith Z.M., Frazier A.E., Francis P.S., Thorburn D.R., et al. N-Acetylcysteine improves mitochondrial function and ameliorates behavioral deficits in the R6/1 mouse model of Huntington’s disease. Transl. Psychiatry. 2015; 5(1): e492. https://doi.org/10.1038/tp.2014.131

33. Gedik S., Erdemli M.E., Gul M., Yigitcan B., Bag H.G., Aksungur Z., et al. Hepatoprotective effects of crocin on biochemical and histopathological alterations following acrylamide-induced liver injury in Wistar rats. Biomed. Pharmacother. 2017; 95: 764–70. https://doi.org/10.1016/j.biopha.2017.08.139


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Khusnutdinova N.Yu., Ryabova Yu.V., Yakupova T.G., Karimov D.O., Smolyankin D.A., Akhmadeev A.R., Khmel A.O., Repina E.F. Changes in the morphofunctional state of the liver under the influence of acrylamide and upon correction with complex compounds of oxymethyluracil in dynamics. Toxicological Review. 2025;33(6):417-425. (In Russ.) https://doi.org/10.47470/0869-7922-2025-33-6-417-425. EDN: npqehr

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ISSN 0869-7922 (Print)
ISSN 3034-4611 (Online)