The assessment of the antihypoxic properties of the complex compound of oxymethyluracil with acetylcysteine in the model of histotoxic hypoxia

Introduction. Oxymethyluracil is an effective antihypoxant in a model of histotoxic hypoxia. Acetylcysteine combines the properties of a toxicotropic nonspecific and toxicokinetic antidote, promotes the synthesis of glutathione in the body.

The aim of the research was a preliminary assessment of the antihypoxic properties of the complex compound of oxymethyluracil with acetylcysteine in the model of histotoxic hypoxia.

Materials and methods. To study the antihypoxic properties, a model of acute histotoxic hypoxia was used. The studied compound was injected into the abdominal cavity of experimental mice three times with an interval of 30 minutes at 100 and 500 mg/kg of body weight, then after 30 minutes the toxicant was introduced. Comparators were oxymethyluracil and acetylcysteine.

Results. The complex compound of oxymethyluracil with acetylcysteine in the model of acute histotoxic hypoxia statistically significantly was established to increase the lifespan of mice at a dose of 500 mg/kg of body weight. A dose of 100 mg/kg of the compound is practically ineffective.

Limitations. The limitations of the study are related with antihypoxic properties of the new complex compound of oxymethyluracil with acetylcysteine previously studied in one model of hypoxia (histotoxic), because oxymethyluracil (as an antihypoxant) is most effective in this experimental model. For a final judgment on the antihypoxic properties of the studied compound, it is necessary to continue studies on other models of hypoxia. In addition, in order to identify possible synergism (potentiation) of the action of oxymethyluracil and acetylcysteine, it seems appropriate to conduct studies to evaluate the antihypoxic effect with their simultaneous administration (in the form of a simple mixture).

Conclusion. A new complex compound of oxymethyluracil with acetylcysteine can be recommended for further wider (preclinical) research as a potential antihypoxant.

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 Vertebrates Used for Experiments or Other Scientific Purposes (ETS No. 123), Directive 2010/63/EC of the European Parliament and of the Council of the European Union of 22.09.2010 on the protection of animals used for scientific research goals.

Contribution:
Repina E.F. — the concept and design of the study, writing the text;
Bakirov A.B. — concept and design of the study, editing;
Gimadieva A.R. — synthesis of 5-hydroxy-6-methyluracil with N-acetylcysteine;
Karimov D.O. — study concept and design, editing;
Kudoyarov E.R., Timasheva G.V. — data collection and processing, statistical analysis;
Khusnutdinova N.Yu., Baigildin S.S., Smolyankin D.A., Muhammadieva G.F. — 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 “Hygienic scientific substantiation of minimizing risks to the health of the population of Russia” for 2016-2020 on topic 3.5, state no. registration AAAA-A16-116022610045-4. 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: May 25, 2022 / Accepted: August 04, 2022 / Published: August 30, 2022