Features of metabolic changes in the liver in experimental animals under chronic exposure to acrylamide and against the background of its preventive correction

Introduction. Acrylamide used industrially is also widely known to be a toxic compound produced during high temperature cooking. Given the danger of its entry into the body, it is important to continue fundamental research to study the mechanism of its toxicity and search for effective ways to correct the disorders caused by it.

The purpose of the research is to study the features of metabolic changes in the liver of rats under conditions of chronic exposure to acrylamide and evaluate the effectiveness of their preventive correction with oxymethyluracil complex compounds.

Materials and methods. Studies were performed on sixty white outbred male rats weighing 180–200 g. Acrylamide was administered intragastrically at a dose of 5 mg/kg of body weight for 90 days. Correction of possible disorders was carried out 1 hour before the administration of the toxicant with complex compounds of oxymethyluracil with ascorbic acid (MG-1), with sodium succinate (MG-2) and acetylcysteine (MG-10). Biochemical parameters were studied after 45 and 90 days of the experiment.

Results. Studies have shown long-term intake of acrylamide at a dose of 5 mg/kg of body weight to lead to metabolic disorders. A statistically significant increase in the activity of the enzymes aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (AP), and superoxide dismutase (SOD) was found. Statistically significant differences in the level of activity of ALT, alkaline phosphatase and SOD for the period of the experiment of 45 days compared with the positive control group were established in the group receiving the MG-10 preparation. After 90 days, in the group of animals treated with the MG-2 preparation, the activity of ALT and alkaline phosphatase decreased significantly. The introduction of the drug MG-10 had a statistically significant effect on ALT activity, reducing it to the level in the negative control group of animals treated with distilled water.

Limitations of the study are related to the correction with complex compounds of oxymethyluracil carried out only in a prophylactic regimen. For the final judgment on their protective effectiveness, it is necessary to introduce them in the accompanying and restorative regimes, as well as to study other biochemical parameters when exposed to acrylamide.

Conclusion. The best protective effect at a period of 45 days was shown by a complex compound of oxymethyluracil with acetylcysteine, at a period of 90 days — a complex compound of oxymethyluracil with sodium succinate.

Compliance with ethical standards. The study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (Protocol dated of 04. 03.2023 No. 01-04), conducted in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experiments or for Other Scientific Purposes (ETS N 123), Directive of the European Parliament and the Council of the European Union 2010/63 /EC of 22.09.2010 on the protection of animals used for scientific purposes.

Contribution:
Repina E.F. — the concept and design of the study, writing the text;
Yakupova T.G. — data collection and processing, statistical analysis, text writing;
Karimov D.O., Bakirov A.B. — study concept and design, editing;
Timasheva G.V. — data collection and processing, statistical analysis;
Shaikhlislamova E.R. — editing;
Gimadieva A.R. — synthesis of complex compounds of oxymethyluracil;
Khusnutdinova N.Yu., Baigildin S.S., Akhmadeev A.R. — collection and processing of material.
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 work was carried out as part of the implementation of the state task for the industry research program of Rospotrebnadzor “Scientific justification of the national system for ensuring sanitary and epidemiological well-being, managing health risks and improving the quality of life of the population of Russia” for 2021-2025. clause 6.1.8, state no. registration 121062100058-8. The synthesis of the 5-hydroxy-6-methyluracil composition 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 No. AAAA-A19-119011790021-4).

Received: June 1, 2023 / Accepted: September 26, 2023 / Published: October 30, 2023