Pathomorphological changes in rat kidneys after exposure to thioacetamide and during treatment with a complex compound of oxymethyluracil and acetylcysteine

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Abstract
Introduction. Thioacetamide belongs to highly toxic compounds that cause significant pathological changes in organs and tissues. In the context of the widespread use of chemicals, the search for effective methods of protecting the body from their negative effects remains an urgent task. The most promising strategy is the development of methods to reduce toxic damage to the body as a result of exposure to chemicals.Material and methods. The study was performed on 56 outbred male rats in a chronic experiment lasting 100 days with an intermediate study of morphological parameters on the 50th day. The animals were divided into 4 groups (2 control and 2 experimental): rats of the second (positive control), third and fourth groups were administered thioacetamide intraperitoneally twice a week at a dose of 50 mg / kg of body weight. The first group of rats (negative control) was administered an equivalent volume of physiological solution in a similar way. One hour before the toxicant, the third experimental group was administered the comparison drug ademetionine at a dose of 25 mg / kg of body weight, the fourth – a complex compound of oxymethyluracil with acetylcysteine at a dose of 500 mg / kg of body weight. The effectiveness of the correction was assessed by pathomorphological changes in the kidneys of rats.Results. In the middle of the experiment, no pathological changes were found in the kidneys of rats of all the studied groups. By the end of the experiment, under the influence of thioacetamide, signs of damage to the renal parenchyma were observed in the form of granular dystrophy, swelling of the cytoplasm of epithelial cells, narrowing of the lumen of the tubules and the formation of protein inclusions. When corrected with a complex compound of oxymethyluracil with acetylcysteine, pathological changes in the kidneys were less pronounced. Morphometric analysis of the cross-sectional area of ​​the proximal tubules and the area of ​​the cell nuclei confirmed the results of histological studies by groups.Limitations. With long-term exposure to thioacetamide, the hepatoprotective efficacy of drugs was assessed primarily by morphological characteristics, but for a more comprehensive assessment of the correction of toxic effects, it is also necessary to take into account biochemical and functional indicators.Conclusion. Chronic administration of thioacetamide to rats at a dose of 50 mg/kg body weight has a nephrotoxic effect, which is reduced by prophylactic administration of ademetionine and a complex compound of oxymethyluracil with acetylcysteine ​​to animals. According to pathomorphological signs, the effectiveness of the nephroprotective effect of the complex compound of oxymethyluracil with acetylcysteine ​​is higher than that of ademetionine.Compliance with ethical standards. The study was approved by the bioethics committee of the Ufa Research Institute of Occupational Medicine and Human Ecology (protocol No. 01-02 dated 08.02.2024).Authors’ contribution: Khmel A.O. – collecting and processing material, writing text; Yakupova T.G., Muhammadieva G.F., Gizatullina A.A., Khusnutdinova N.Yu. – collecting and processing material; Ryabova Yu.V., Repina E.F. – editing; Karimov D.O. – research concept and design, statistical analysis. All co-authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.Conflict of interests. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.Funding. The work was carried out as part of the state assignment 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. Received: April 2, 2025 / Revised: May 5, 2025 / Accepted: November 25, 2025 / Published: January 15, 2026

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