Experimental assessment of the protective effect of hydroxymethyluracil complex compounds under extreme exposure to acrylamide

Introduction. Acrylamide is widely used in industry. Considering the potential danger of acute acrylamide poisoning, it seems urgent to search for new effective ways to protect and increase the body’s resistance to extreme exposure.

The purpose of the study is to conduct a comparative assessment of the protective effect of hydroxymethyluracil complex compounds when administering moderate lethal doses of acrylamide to laboratory animals.

Materials and methods. The subacute experiment was conducted on thirty outbred male rats weighted of 189–194 g. For 14 days, a toxicant was administered intragastrically at a dose of 20 mg per kg of body weight, then a single dose of 200 mg per kg of body weight was administered. Animals received complex compounds of hydroxymethyluracil with ascorbic acid and sodium succinate (50 mg per kg body weight), with acetylcysteine (500 mg per kg body weight) one hour before acrylamide. Against the background of the administration of complex compounds without acrylamide to the animals. Then one week later, an analysis of the mortality was carried out, and the weight coefficients of the liver and kidneys were determined in the surviving animals.

Results. When acrylamide was administered to animals at the level of average lethal doses, 4 out of 6 animals died in the positive control group. In the groups in which animals received, in addition to acrylamide, the compound of hydroxymethyluracil with ascorbic acid and sodium succinate, the death rate was 2 out of 6 rats. Among the animals that received the compound of hydroxymethyluracil with acetylcysteine, no mortality was recorded within 7 days, as in the group negative control.

Limitations of the study are that the protective effect of hydroxymethyluracil complex compounds was assessed only on one species and gender of laboratory animals.

Conclusion. The complex compound of hydroxymethyluracil with acetylcysteine has a significant protective effect on male rats under extreme exposure to acrylamide at the level of moderate lethal doses. For a more complete understanding of the mechanism of action and a final judgment about the protective properties of the being studied complex compounds, it is necessary to continue research with analysis of changes in other indicators of the health status of laboratory animals.

Compliance with ethical standards. The study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology, 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:
Khusnutdinova N.Yu. — research design, collection and processing of material, writing the text;
Repina E.F. — concept and design of the study, writing the text;
Yakupova T.G. — data collection and processing, statistical analysis;
Gimadieva A.R. — synthesis of complex compounds of oxymethyluracil;
Karimov D.O. — concept and design of the study, editing;
Shaykhlislamova E.R. — editing;
Bakirov A.B. — concept and design of the study, editing;
Karimov D.D., Baygildin S.S., Chernyaeva E.Yu. — 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.

Acknowledgment. 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: September 21, 2023 / Accepted: November 15, 2023 / Published: December 8, 2023