The effectiveness of the use of oxymethyl uracil on the model of acute alcohol intoxication

Introduction. Considering the prevalence of acute alcohol poisoning in Russia, it seems urgent to search for new effective means of correcting them. Along with taking measures to remove ethanol from the body, pathogenetic correction is effective. Oxymethyluracil and its derivatives have proven to be effective hepatoprotectors in various experimental models of liver damage. 

The aim of the research was the evaluation of the effectiveness of oxymethyl uracil on the model of acute alcohol intoxication. 

Material and methods. On the model of acute toxic liver injury of laboratory animals with ethanol, the efficiency of correction of pathological changes with oxymethyl uracil was studied compared to the drug “Mexidol”. A complex of biochemical, morphological and genetic studies was carried out.

Results. The morphological studies showed that the correction with oxymethyluracil was more effective at both time points than the drug “Mexidol”, which was manifested in a lower intensity of damage to the liver parenchyma. In the group that received oxymethyluracil, a restoration of the frequency of expression of the Chek 1 gene was observed both after 24 and 72 hours. Upon acute exposure to ethanol, a slight decrease in the level of RIPK1 gene expression was observed. The level of expression of this gene decreased most significantly during the correction of oxy methyl uracil. A decrease in the frequency of expression of this gene can indicate a slowdown in necrosis processes and suppression of reactive oxygen species production in liver cells and, consequently, a curative effect of oxymethyluracil in this type of intoxication.

Conclusion. Based on the complex biochemical, morphological and genetic studies carried out, it can be concluded that under acute exposure to ethanol, the corrective effect of oxymethyl uracil is more pronounced than Mexidol (ethylmethylhydroxypyridine succinate).

Contribution:
Bakirov A.B. — the concept and design of the study;
Repina E.F. — the concept and design of the study, writing a text;
Karimov D.O. — the concept and design of the study, collection and processing of material, editing;
Baygildin S.S., Timasheva G.V. — collection and processing of material, statistical processing;
Gimadieva A.R. — oxymethyluracil synthesis;
Yakupova T.G., Khusnutdinova N.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.

Acknowledgement. The work was carried out at the expense of subsidies for the implementation of a state task within the framework of the sectoral research program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing (Rospotrebnadzor) “Hygienic scientific substantiation of minimizing risks to the health of the population of Russia” for 2016-2020 on topic 3.5, the state no. registration AAAA-A16-116022610045-4. The synthesis of the 5-hydroxy-6-methyl uracil composition was carried out under 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).

Conclusion of the bioethical commission: the study was approved by the bioethical commission of the “Ufa Research Institute of Occupational Health and Human Ecology”, carried out per the European Convention for the Protection of Vertebrate Animals Used for Experiments or Other Scientific Purposes (ETS N 123), the directive of the European Parliament and the Council of the European Union 2010/63 / EU of 22.09.2010 on the protection of animals used for scientific purposes.

Received: June 8, 2021 / Accepted: September 28, 2021 / Published: November 30, 2021