Experimental evaluation of the effectiveness of prophylactic correction of thioacetamide hepatotoxicity during long-term exposure

Introduction. Thioacetamide is an organosulfur compound widely used in industry and as a model toxicant in experiments on laboratory animals. Despite certain successes in finding ways to correct toxic changes in the liver using pharmacological agents, surgical intervention or exposure to physical factors, the effectiveness  of treating liver fibrosis and cirrhosis is currently low.

Purpose of the work is to evaluate the effectiveness of prophylactic correction of thioacetamide hepatotoxicity with long-term exposure.

Materials and methods. The experiment were conducted over 100 days on 56 outbred conventional male rats. Thioacetamide was administered intraperitoneally twice a week at a dose of 50 mg/kg b.w. The carrier and control substance were saline. Correction was performed 1 hour before the toxicant ademetionine and a complex compound of 5-hydroxy-6-methyluracil with acetylcysteine. Biochemical, genetic, and morphological parameters were studied at periods of 50 and 100 days. Statistical analysis was performed using SPSS Statistics 21.0 software (IBM, USA).

Results. When exposed to thioacetamide, the activity of the studied enzymes increased. The results of histomorphological studies at two time points of the experiment indicate the effect of thioacetamide on the rat liver to manifest in the form of mixed (postnecrotic and atrophic) cirrhosis. A tendency towards an increase in the expression of the Casp7 gene was established. Preventive administration of corrective drugs had a noticeable effect on the activity of the gamma-glutamyl transferase enzyme. Ademetionine was more effective at 50 days, and MG-10 at 100 days. With prophylactic administration of MG-10, the growth of fibrous tissue in the liver and its infiltration with leukocytes were visualized to a lesser extent.

The limitations of the study are that with long-term exposure to TAA, the hepatoprotective efficacy of the drugs was assessed only for two apoptosis genes. For a more complete assessment of the effectiveness of the correction, it is necessary to compare the results with other indicators of the toxic effect of TAA.

Conclusion. Thioacetamide, when administered for a long time at a dose of 50 mg/kg b.w., causes a significant hepatotoxic effect, manifested in pathological changes in biochemical, morphological, and genetic parameters. Prophylactic administration of a complex compound of oxymethyluracil with acetylcysteine ​​​​has  a greater hepatoprotective effect.

Compliance with ethical standards. the study was approved by the bioethical commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (the meeting report No. 01–02 dated 08.02.2024), 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.

Contributions:
Repina E.F. – study concept and design, statistical analysis, writing the text;
Gimadieva A.R. – synthesis of a complex compound of oxymethyluracil with acetylcysteine;
Karimov D.O., Ryabova Yu.V. – study concept and design, editing;
Kulagin E.A., Smolyankin D.A., Gizatullina A.A., Yakupova T.G., Karimov D.D. – data collection and processing.
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.

Funding. The work was carried out as part of the state assignment for the industry research program of the Federal Service for Supervision in Protection of the Rights of Consumer and Man Wellbeing “Scientific substantiation of the national system for ensuring sanitary and epidemiological welfare, health risk management and improving the quality of life of the population of Russia” for 2021–2025. p. 6.1.8, state. Registration No 121062100058-8.

Received: January 29, 2025 / Accepted: March 26, 2025 / Published: July 31, 2025

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