Aleksandra Olegovna Khmel'

Objective - To conduct a comparative evaluation of the efficacy of prophylactic correction using ademetionine and a complex of oxymethyluracil with N-acetylcysteine in a model of thioacetamide-induced toxicity. Materials and Methods. The study was performed on 56 male rats. Toxicity was induced by intraperitoneal administration of thioacetamide at 50 mg/kg body weight twice weekly for 100 days. The animals were assigned to four groups: negative control, positive control, and two experimental groups receiving thioacetamide in combination with either ademetionine or the oxymethyluracil-N-acetylcysteine complex. The corrective agents were administered one hour prior to the toxicant. On days 50 and 100, serum and urine biochemical parameters were assessed, along with gene expression in the liver and kidneys related to antioxidant defense, the glutathione system, apoptosis, and the cell cycle. Histological and morphometric tissue analyses were also performed. Results. The positive control group confirmed the development of chronic toxic hepatitis with progressive liver fibrosis. The use of a complex of oxymethyluracil and acetylcysteine demonstrated superiority over ademetionine in preventing long-term outcomes, with ademetionine primarily exerting an early metabolic effect without affecting the progression of liver fibrosis or structural tissue remodeling in the later stages. Regarding the kidneys, morphometric stress was observed by the end of the treatment period, most noticeable in the positive control group and during prophylactic administration of ademetionine. Conclusion. Under the conditions of intoxication considered, both compounds demonstrated a certain ability to modify late structural outcomes. The complex compound of oxymethyluracil with acetylcysteine demonstrated a more favorable profile at the late stage, while ademetionine was more effective at the early stages. These findings highlight the potential of antioxidant-targeted strategies for the prevention of adverse outcomes in chronic toxic injury.

Introduction. Disruptions in circadian coordination are accompanied by reduced attention, increased fatigue, and a higher likelihood of metabolic and cardiovascular diseases. At petrochemical plants, workers are exposed to chemical factors that, in themselves, can cause damage to the nervous system and disrupt hormonal and metabolic regulation. The impact of the combined effects of chronic circadian stress on workers in chemical plants is an urgent task for modern occupational health.The study aims to determine the specific effects of the combined exposure to acrylamide and circadian stress on the behavioral and motor functions in rats, as assessed in the elevated plus maze test, the grip strength test, and the motor activity test.Materials and methods. Scientists conducted an experiment on white outbred male Wistar rats weighing 190–200 g and aged 6 weeks, kept under standard vivarium conditions with free access to water and food and under a regulated light regime. The researchers divided the animals into 4 groups. For one month, the rats in the experimental groups received acrylamide and were exposed to circadian stress. Upon completion of the experiment, the authors conducted a behavioral assessment, which included the elevated plus maze test to analyze anxious behavior, a grip strength test to assess muscle strength, and a motor activity test to characterize the level of motor activity.Results. The combined exposure to acrylamide and circadian stress led to a decrease in the motor and exploratory activity of rats, an increase in the time during which the animals froze, and the manifestation of anxious behavior in an elevated cross shaped maze. In animals from this group, the researchers observed a decrease in the distance traveled, the speed of movement, the time spent in a mobile state, and the number of entries into the open sections of the maze. In the "Grip Strength" test, the researchers recorded the maximum peak strength in rats from group II, while no pronounced changes were observed with combined exposure.Limitations. The study was conducted on male Wistar rats, which does not allow assessing sexual dimorphism in the response to combined exposure. The small group size (n=7) limits statistical power in multiple comparisons and increases the variability of the estimates. A single dose of acrylamide and a fixed exposure period were used, which limits the analysis of dose–effect and time–effect relationships, as well as the assessment of the reversibility of the observed effects. The applied model of circadian stress was developed by Salgado Delgado R. et al. is not a classical one, and the presented conclusions are based solely on the evaluation of behavioral test results. The model conditions differ from long term cumulative exposure in real production conditions, so quantitative risk assessments cannot be directly applied to humans without additional research.Conclusion. Against the background of combined exposure to acrylamide and circadian stress in rats, the authors observed more pronounced changes in motor and exploratory activity than in the case of isolated exposure to these factors.Ethics. Protocol of the Bioethics Committee Meeting of the Ufa Research Institute of Occupational Medicine and Human Ecology, No. 01-02, dated February 8, 2024. Throughout the study, animals were maintained under standard conditions with twelve hours of artificial lighting during the day, a humidity level of 30–70%, and an air temperature of 20–25°C. For groups II and IV, circadian stress was modeled by daily forced activity during daylight hours, which led to a disruption of the animals' usual daily routine. Animal manipulations were carried out in full compliance with regulatory documents, including the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986).Contributions:Gizatullina A.A. — data collection and processing, writing the article text;Yakupova T.G. — participation in conducting experiments, data collection and processing;Khmel A.O. — participation in conducting experiments;Smolyankin D.A. — participation in conducting experiments;Karimov D.D. — data collection and processing;Mukhammadieva G.F. — data collection and processing;Karimov D.O. — development of the concept and study design, statistical data processing;Ziatdinova M.M. — text editing, literature analysis.Funding. The industry specific research program of Rospotrebnadzor for 2021–2025 "Scientific substantiation 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", topic 6.9.1.2 "Study of the impact of chemical occupational factors under conditions of chronic stress", No. NIOCTR I124021200153–3.Conflict of interest. The authors declare no conflict of interest.Received: 12.08.2026 / Accepted: 08.10.2026 / Published: 03.11.2026

Introduction. Cadmium intoxication remains a pressing issue in ecology and occupational health, especially in conditions of industrial pollution. The development of accessible and safe means of protection against the toxic effects of heavy metals is of great importance for reducing occupational and environmental health risks.The study aims to investigate the effect of pectin based on hydroxymethyluracil on the expression of metallothionein genes and the histological structure of the rat liver under chronic cadmium intoxication.Materials and methods. The researchers conducted a study on 60 female outbred rats weighing 190–220 g, divided into 5 groups of 12 animals each, depending on the treatment regimen, which included CdCl₂ (0.1 mg/kg) and pectin based on oxymethyluracil (50 mg/kg). The authors used liver tissue samples as the research material; the level of transcription of metallothionein genes was determined in the homogenate using quantitative polymerase chain reaction (qPCR), and histological examination of liver sections was also carried out to assess the degree of damage.Results. Chronic cadmium intoxication caused a slight increase in the expression of the Mt1 gene (0.2±0.34; p=2.764) and a moderate decrease in the expression of the Mt2 gene (–0.39±0.48; p=0.959), without significant activation of the Mt3 gene (–0.78±0.47; p=0.622). The use of oxidized pectin led to selective modulation of metallothionein expression. Mt1 expression was significantly reduced in all pectin-based OMU groups compared to the positive control group (group 3 (–1.6±0.57; p=0.044, group 4 (–1.49±0.29; p=0.002, group 5 (–1.36±0.41; p=0.028)), with no significant differences between regimens (p>0.05), indicating stable suppressive effect of pectin regardless of the time of application. Mt2 expression was significantly suppressed in all correction groups compared to both positive and negative control groups (group 3 (–2.59±0.57; p<0.001 vs K–; p=0.015 vs K+), group 4 (–2.02±0.21; p<0.001 vs K–; p=0.011 vs K+), group 5 (–2.45±0.35; p<0.001 vs K–; p=0.004 vs K+)). In contrast, Mt3 expression showed significant stimulation by oxidized pectin, especially with long-term treatment including recovery (1.32±0.39; p=0.005 vs K+, p=0.043 vs K–). In the same group, histology revealed preserved lobular architecture, absence of congestion, and minimal infiltrates, compared to inflammation, fibrosis, and necrosis in the positive control group.Limitations. Only three MT genes (Mt1, Mt2, Mt3) have been studied — this does not provide a complete range of isoforms or cover other stress genes (Nrf2, HO 1, ZIP8). There is no long term observation (lasting more than 4 months) to assess the persistence of the effect; no quantitative measurement of cadmium content in liver tissue has been carried out; biochemical markers of liver damage have not been studied.Conclusion. In the study, pectin based on OMU demonstrated a corrective potential in the context of cadmium hepatotoxicity, normalizing the expression of the Mt1 and Mt2 genes, activating the expression of the Mt3 gene, and protecting the liver’s histoarchitectonics from damage.Ethics. The study was conducted in accordance with the protocol of the bioethics commission of the Federal Budgetary Institution "Ufa Research Institute of Occupational Health and Human Ecology", No. 01-1, dated January 22, 2025, in accordance with the recommendations of the Ministry of Health of the Russian Federation, the European Convention ETS No. 123, and WHO guidelines. Euthanasia was carried out using controlled CO₂ administration, followed by decapitation to collect biomaterial (Order No. 755 of the USSR Ministry of Health dated August 12, 1977).Contributions:Ziatdinova M.M. — data collection and processing, text writing;Kudoyarov E.R. — editing;Khmel A.O. — material collection and data processing;|Smolyankin D.A. — material collection and data processing;Yakupova T.G. — material collection and data processing;Karimov D.D. — data processing and statistical processing;Karimov D.O. — research concept and design, statistical processing;Zimin Yu.S. — synthesis of pectin based on OMU;Borisova N.S. — synthesis of pectin based on OMU.All co authors — approval of the final version of the article, responsibility for the integrity of all parts of the article.Funding. The sectoral research program of Rospotrebnadzor for 2021–2025, "Scientific substantiation 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", topic 6.1.9. "Experimental substantiation of highly sensitive markers of the effects of heavy metals on the body and the development of preventive measures", No. R&D No. 121062100057-1.Conflict of interest. The authors declare no conflict of interest.Received: 06.05.2026 / Accepted: 05.08.2026 / Published: 11.09.2026

Aluminum hydroxide [Al(OH3] is widely used in medicine as a component of antacids and as an adjuvant in vaccines. However, its safety during chronic alimentary exposure remains a subject of debate, particularly in the context of potential accumulation in the central nervous system and neurotoxic effects. Aluminum is a common metal, the effects of which on the central nervous system raise serious scientific concerns. The aim of this study was to comprehensively evaluate the effects of chronic aluminum hydroxide administration on neurobehavioral characteristics, histomorphological structure, and essential element metabolism in the rat brain. A chronic alimentary exposure model using varying doses of aluminum was used. The results showed dosedependent accumulation of aluminum in the brain and a statistically significant increase in magnesium levels at high doses. Changes in iron levels were inconsistent, while calcium levels remained stable. Behavioral tests revealed no significant cognitive impairment, indicating that the animals retained cognitive resilience during chronic exposure to the selected doses of aluminum. The histological analysis revealed no signs of significant neurodegeneration or gross structural pathologies in the brain tissue samples. A significant limitation of this phase of the study is the lack of standardized sampling of identical cortical areas for all animals, which precludes quantitative comparative conclusions regarding neurodegenerative changes. Thus, the data obtained expand our understanding of the multifaceted neurotoxic effects of aluminum during chronic exposure and highlight the need for further research into the mechanisms of its action on brain function and structure.

Introduction. The ovaries are among the key organs of the female reproductive system, responsible for oocyte formation and maturation, as well as the synthesis of sex hormones. Disruptions in these processes, caused by various environmental contaminants, can lead to a range of pathological conditions. Assessing the distribution of plastic microparticles of different sizes is thus critically important for predicting potential reproductive health risks in women.The aim of our study. To determine and compare the characteristics of accumulation of plastic microparticle (100, 500, and 1000 nm) in the ovaries of female Wistar rats following acute systemic administration, using a specially developed software for automated quantitative analysis of fluorescent images.Material and methods. Twelve female Wistar rats were divided into four groups; each group received an intracardiac injection of a 0.5 mL suspension of fluorescent polystyrene microparticles (MP) with diameters: 100, 500, and 1000 nm) or saline (control). Accumulation of microplastic in ovarian tissue was evaluated by fluorescent microscopy with a descriptive approach and a software designed for quantitative assessment of microparticles and their conglomerates. Data were analyzed using the Bootstrap method with Holm–Bonferroni correction; differences were considered significant at p < 0.05.Results. Only occasional background signals were registered in the control group. All experimental groups demonstrated a significant increase in both the number and total area of microparticles compared to control (p < 0.05), with the highest overall accumulation found in the “MP 1000” group. Smaller particles (100 nm) displayed a pronounced tendency to form large conglomerates, whereas 1000 nm particles were primarily present as individual deposits.Limitations. The investigation was limited to examining the distribution of three sizes of plastic MP within a single experimental series and a single animal species (laboratory rats), without accounting for the estrous cycle phase.Conclusion. Even a short-term exposure to plastic MP can result in their accumulation in ovarian tissue, with the location pattern and the likelihood of conglomerate formation depending on the particle size.Compliance with ethical standards. All experiments in this study were conducted in accordance with European Convention standards for the protection of vertebrate animals used for research and other scientific purposes. The study protocol was approved by the local ethics committee (Approval No. 01-02 from February 8, 2024).Contribution: Ryabova Yu.V. – research concept and design, writing the text, preparing figures; Muhammadieva G.F. – conducting the experiment, scientific editing of the text; Valova Ya.V. – research concept and design, data collection and processing; Khmel A.O. – conducting the experiment, data collection and processing; Repina E.F. – research concept and design; Karimov D.O. – research concept and design; Ahmadeev A.R., Khusnutdinova N.Yu., Kudoyarov E.R. – conducting the experiment. 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 study was carried out within the framework of the sectoral research program of the Federal Service for Surveillance on Consumer Rights Protection and Human Wellbeing for 2021–2025.Received: April 4, 2025 / Accepted: October 15, 2025 / Published: April 17, 2026

Introduction. Chronic stress and paracetamol exposure are among the most relevant factors affecting neurochemical and molecular processes in the brain in modern humans. Excessive activation of inflammatory and oxidative pathways during chronic psychosocial stress can lead to a decrease in the expression of neuroprotective and antioxidant genes, exacerbating the neurotoxic effects of drugs such as paracetamol.Objective. To assess the effect of chronic unpredictable stress and oral administration of paracetamol, as well as their combined effect on the morphological state of the brain and on the expression of genes of the antioxidant system and neurotrophic factor in the hippocampus in rats.Materials and methods. The experiment was conducted on forty eight rats (males and females in equal numbers), divided into four groups: control, chronic stress, paracetamol, combined exposure to stress and paracetamol. A complex of various stressors was used to model chronic stress. Paracetamol was administered orally at a dose of 1000 mg/kg. The morphological state of the hippocampus was assessed histologically, gene expression - by quantitative real-time PCR. Statistical analysis included bootstrapping and correction for multiple comparisons using the Holm-Bonferroni method.Results. Macroscopic and histological examination of the rat brain showed the preservation of the normal anatomical structure and integrity of the hippocampal tissues in all groups. Statistical analysis of gene expression showed animals treated with paracetamol (groups III and IV) to show a significant decrease in the mRNA levels in the Sod1 and Bdnf genes in the hippocampus compared to the control and the group exposed to stress only (group II). The expression level of Sod1 and Bdnf was significantly lower in both males and females in these groups (p = 0.001). For the Hmox1 gene, a significant decrease in expression was found only in males in the paracetamol-treated group, while no changes were noted in females.Limitations. Laboratory animals of the same biological species were used for the experiment, and the toxicant was used in only one concentration.Conclusion. Thus, paracetamol, both in isolated use and in combination with chronic stress, has a more pronounced inhibitory effect on the expression of key genes of antioxidant protection and neurotrophic support than stress alone.Compliance with ethical standards. Date of the meeting of the bioethics commission of theUfa Research Institute of Occupational Medicine and Human Ecology dated 02/08/2024 No. 01–02. Throughout the study, the animals were kept in standard conditions with 12-hour artificial lighting during the daytime, a relatively constant level of humidity (30–70%) and an air temperature of 20–25 °C. All animal manipulations were carried out in strict compliance with the rules prescribed in the basic regulatory documents, including the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986) and the Helsinki Declaration on the Humane Treatment of Animals.Contributions: Gizatullina A.A. – concept and study design, material collection and processing, statistical analysis, manuscript writing; Valova Ya.V. – material collection and processing, statistical analysis; Mukhamadieva G.F. – editing; Karimov D.O. – concept and study design, statistical analysis; Karimov D.D. – material collection and processing; Ryabova Yu.V. – material collection and processing; Khusnutdinova N.Yu. – material collection and processing; Khmel A.O. – material 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. Industry research program of Rospotrebnadzor for 2021–2025 “Scientific substantiation of the national system for ensuring sanitary and epidemiological welfare, managing health risks and improving the quality of life of the population of Russia”, on the topic: 6.9.1.2 “Study of the impact of chemical production factors under conditions of chronic stress” No. NIOKTR I124021200153-3.Received: April 30, 2025 / Revised: July 9, 2025 / Accepted: October 15, 2025 / Published: April 17, 2026

Aluminum is a common chemical element, and low-dose subchronic exposure can cause latent metabolic disturbances. The aim of this study was to evaluate the dose-dependent effects of long-term oral administration of aluminum hydroxide on metal accumulation and mineral homeostasis in rat liver. The experiment was conducted on male Wistar rats that were administered an aqueous suspension of Al(OH)₃ at doses of 0.015, 0.15, and 1.5 mg/kg body weight for 28 days. The contents of aluminum, calcium, magnesium, and iron in the liver were determined by atomic absorption spectrometry. Aluminum accumulation in the liver was found to be nonlinear: the maximum concentration was detected at the minimum dose, whereas it increased with increasing dose. Exposure to aluminum hydroxide was accompanied by pronounced disturbances in mineral homeostasis, as evidenced by changes in calcium content, a decrease in magnesium concentration, and a dose-dependent decrease in iron level. The obtained data indicate the ability of aluminum hydroxide to cause significant disturbances in elemental metabolism in the liver even at low levels of subchronic exposure, emphasizing the need for further study of the mechanisms of its toxic action and assessment of potential health risks.

Introduction. In conditions of high chemical load and the increasing prevalence of neurodegenerative diseases, it seems relevant to study the effect of the most common food additives on cognitive functions.The aim is to study the effect of increased doses of sodium benzoate, potassium sorbate, and ascorbic acid on the cognitive functions in white laboratory rats in a rectangular maze, taking into account the ability of the animal’s body to recover after exposure to this mixture.Materials and methods. The study of changes in the chemical composition of the brain under the influence of a mixture of food additives at different dose levels by capillary electrophoresis was carried out in a series of experiments using laboratory mice; rats were used to assess changes in cognitive function under the influence of a mixture of food additives. For statistical processing of the obtained data, the IBM SPSS Statistics 21 package was used. Comparison of groups was carried out using one-way variance analysis.Results. Dietary supplements have been shown to affect the chemical composition of the brain in mice by altering the concentrations of ascorbic (AA), sorbic (SA) and benzoic acids (BA). An increase in the concentration of AA in the brain was observed in all groups receiving additives, especially on day 30 of the experiment. The maximum concentration of SA was recorded at different time points of the experiment (day 5, day 12) depending on the dose of preservatives. An increased content of BA was shown on day 12 of the experiment. During the initial training phase, the supplement mixture improved the rats’ cognitive performance, reducing maze time in both sexes. On day 8, differences in the speed of completing the maze were noted between females and males (p=0.026). After the recovery stage, a deterioration in performance was recorded in both sexes, but more pronounced in females. On day 13, the best results in completing the maze were recorded in female rats.Limitations. The study was conducted once on two types of laboratory rodents. The results obtained on rats and mice cannot always be directly transferred to humans.Conclusions. Changes in the chemical composition of the brain in animals were observed by the 30th day of the experiment, which indirectly correlates with some changes in cognitive functions. A neuroprotective effect of ascorbic acid is assumed, but further studies are needed to clarify the potential mechanism of the processes.Compliance with ethical standards. Date of the meeting of the bioethics commission of the Ufa Research Institute of Occupational Medicine and Human Ecology 02. 08.2024 No. 01-02. The studies were carried out in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS N 123), Directive of the European Parliament and of the Council of the European Union 2010/63/EU of 09.22.2010 on the protection of animals used for scientific purposes.Contribution: Smolyankin D.A., Ryabova Yu.V. ‒ study concept and design, collection and processing of materials, statistical processing of data, writing, editing; Khusnutdinova N.Yu., Repina E.F., Valova Ya.V., Yakupova T.G., Khmel A.O. ‒ collection and processing of materials, editing; Kurilov M.V. ‒ collection and processing of materials, statistical processing of data, editing; Karimov D.O. ‒ study concept and design, statistical processing of data, writing, editing; Karimov D.D. ‒ collection and processing of materials, statistical processing of data; Akhmadeev A.R. ‒ 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.Funding. The work was carried out using funds from a subsidy for the implementation of a state assignment within the framework of the industry research program of Rospotrebnadzor for 2021–2025. “Scientific substantiation 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”, paragraph 6.1.8 “Scientific substantiation of approaches to assessing the toxic effect of xenobiotics based on cellular technologies and model objects”, registration number: 121062100058-8.Received: February 2, 2025 / Accepted: June 26, 2025 / Published: March 13, 2026

Introduction. Acrylamide is widely used in various industries and is recognized as a toxic compound. Considering the potential risks of its entry into the human body, further research is required to understand the mechanisms of its toxicity and to develop effective approaches for correcting pathological conditions caused by its exposure.The purpose of the study was to evaluate changes in the morphofunctional state of the liver under the influence of acrylamide and correction with oxymethyluracil complexes in dynamics, based on biochemical, genetic and morphological parameters.Material and methods. The experimental study was conducted on outbred male rats, which were administered acrylamide intragastrically at a dose of 5 mg/kg body weight over three months. Preventive correction was performed using oxymethyluracil complexes. Biochemical, genetic, and morphological studies were performed.Results. The studies revealed that after 1.5 and 3 months, the activity of hepatic enzymes significantly increased, and minor changes were observed in the liver parenchyma. The expression of glutathione system genes decreased mid-experiment and increased by the end. Oxymethyluracil complexes demonstrated a certain hepatoprotective effect.Limitations. For a deeper study of this problem, it is necessary to consider the effect of different dosages of the hepatotoxicant and the protective effectiveness of compounds in other modes of exposure to the body.Conclusion. Long-term exposure to acrylamide at a dose of 5 mg/kg body weight had a hepatotoxic effect, manifested by increased activity of cytolysis marker enzymes, bidirectional changes in the expression of genes involved in detoxification processes depending on exposure duration, and, to a lesser extent, histological changes in organ structure. Complex compounds of oxymethyluracil exhibited hepatoprotective effects, with their corrective efficiency ranked as follows: MG-10 > MG-2 > MG-1.Compliance with ethical standards. The study was approved by the Bioethical Commission of the Ufa Research Institute of Occupational Medicine and Human Ecology (Protocol No. 01-10 dated 09.10.2024).Authors’ contribution: Khusnutdinova N.Yu. – conducting research, collecting and processing material, writing text; Ryabova Yu.V. – material processing, text writing; editing; Yakupova T.G. – conducting research, data collection and processing, statistical analysis; Karimov D.O. – research concept and design, editing; Smolyankin D.A., Akhmadeev A.R., Khmel A.O. – data collection and processing, statistical analysis; Repina E.F. – data collection and processing, editing. All co-authors – approval of the final version of the article, responsibility for the integrity of all parts of the article.Acknowledgments. The authors express their gratitude to Alfiya Raisovna Gimadieva A.R., Candidate of Chemical Sciences, Senior Researcher at the Laboratory of Pharmacophore Cyclic Systems of the Ufa Institute of Chemistry, Ufa Federal Research Center of the Russian Academy of Sciences, for the development and synthesis of oxymethyluracil complexes.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 substantiation of the national system for ensuring sanitary and epidemiological welfare, managing health risks and improving the quality of life of the population of Russia” for 2021-2025, (clause 6.1.8), state registration number 121062100058-8. The synthesis of complex compounds of oxymethyluracil 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 Number AAAA-A19-119011790021-4).Received: May 24, 2025 / Revised: June 22, 2025 / Accepted: November 25, 2025 / Published: January 15, 202

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