Алина Анваровна Гизатуллина

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. Prooxidants are substances capable of inducing oxidative stress through the generation of reactive oxygen species. Hydrogen peroxide belongs to the class of oxidizing agents, the biological effect of which is determined not only by the dose but also by the state of the cell’s antioxidant and detoxification systems. The liver, being the central organ for the biotransformation of xenobiotics, is of interest for assessing early molecular signs of adaptation to chronic peroxidative exposure. Developing specific approaches to assessing the prooxidant activity of chemical substances is an urgent task in preventive toxicology.The study aims to develop a specific test system for assessing the pro oxidant activity of toxicants based on the method of analyzing gene expression in rat liver and to demonstrate its capabilities using the example of determining the threshold of chronic effect of hydrogen peroxide when administered orally.Materials and methods. Female outbred rats received hydrogen peroxide by gavage for 6 months at doses of 0.05, 0.5, 5 and 50 mg/kg. Control animals received distilled water. Gene expression in liver samples was assessed by real-time quantitative RT-PCR and normalized to Gapdh. An integral GST-index was calculated as the mean expression of Gstp1, Gstt1 and Gstm.Results. At exposure levels of 0.05 and 0.5 mg/kg, no statistically significant changes in the expression of GST genes were detected. At a dose of 5 mg/kg, a significant increase was observed in NFE2L2 to 1.51±0.28, Gstp1 to 1.97±0.07, Gstt1 to 2.04±0.12, and Gstm to 2.31±0.14 relative units. The GST index increased from 1.00±0.06 in the control group to 2.11±0.06 at 5 mg/kg and to 4.22±0.08 at 50 mg/kg. The calculation of the benchmark dose for a twofold increase in the GST index yielded BMD=4.06 mg/kg and BMDL=2.65 mg/kg.Limitations. The study was conducted using a single experimental model and a single pro oxidant, which limits the direct extrapolation of the results to other compounds. The gene expression analysis reflected the mRNA level and did not include the determination of the corresponding proteins and the activity of GST enzymes. The obtained threshold values require confirmation in independent experimental series.Conclusion. The obtained data indicate a stepwise activation of the NFE2L2/GST axis in the liver under chronic exposure to hydrogen peroxide, which makes it possible to use the analysis of gene expression in rat liver as a specific test system for assessing the pro oxidant activity of chemicals during their hygienic regulation. A dose of 5 mg/kg can be considered as the molecular threshold of a compensated adaptive response, at which the enzymes of the second phase of detoxification are activated without signs of total transcriptional decompensation.Ethics. The experimental study was conducted in compliance with the necessary regulatory acts (the 2013 Helsinki Declaration, GOST 33044–2014 "Principles of Good Laboratory Practice"; Order of the Ministry of Health of the Russian Federation No. 188n dated April 1, 2016, "Rules of Good Laboratory Practice"). The study protocol was approved by the Ethics Commission of the F.F. Chernousov Federal Research Center for Hygiene. "Erisman" of Rospotrebnadzor (minutes of meeting No. 7 dated October 21, 2024).Contributions:Karimov D.O. — research concept and design, collection and processing of experimental data, writing the text;Tonshin A.A. — research concept and design, text writing;Bidevkina M.V. — research concept and design, conducting experiments, text writing;Vinogradova A.I. — research concept and design, conducting experiments, collecting and processing experimental data;Ryabova Yu.V. — collection and processing of experimental data;Gizatullina A.A. — collecting and processing experimental data;Akhmadeev A.R. — collecting and processing experimental data;Ziatdinova M.M. — collecting and processing experimental data.Funding. The study had no funding.Conflict of interest. The authors declare no conflict of interest.Received: 15.09.2026 / Accepted: 17.09.2026 / Published: 09.10.2026

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.

The immune system is one of the most sensitive targets of the stress response, as reflected by alterations in lymphoid organs and hematological parameters. Paracetamol, one of the most widely used analgesics, is traditionally studied as a hepatotoxic agent; however, its effects on immunohematological parameters remain insufficiently explored, especially in combination with chronic stress. The aim of the study was to assess the effects of 28-day administration of paracetamol (1000 mg/kg), including under conditions of chronic unpredictable stress, on body weight, thymus and spleen weight coefficients, and hematological parameters in male and female rats. In males, chronic stress caused a significant decrease in leukocyte count (to 5,7×10 ⁹ /L; p=0,001), whereas paracetamol increased leukocyte levels compared to stress alone (p=0,001). Paracetamol reduced hemoglobin levels (129,5 g/L), while in combination with stress, hemoglobin was increased (141,1 g/L; p=0,001). In females, these changes were not observed; however, a significant decrease in platelet count was detected in all experimental groups (p=0,001). The thymus weight coefficient in females decreased after paracetamol administration (1,08; p 0,01), whereas in males it remained unchanged. A reduction in spleen weight coefficient was observed only in males under stress and combined exposure (p≤0,02).The data indicate a sex-dependent pattern of immunohematological changes associated with paracetamol administration, both alone and in combination with chronic stress. At the same time, the absence of endocrine parameter assessment does not allow the observed differences to be unequivocally interpreted as evidence of a stress-protective effect of paracetamol; these findings require further investigation with the inclusion of markers of hypothalamic-pituitary-adrenal and gonadal regulation.

Objective - The aim of the study was to experimentally assess the preventive effect of a complex of oxidized pectin and oxymethyluracil on chronic aluminum-induced hepatotoxicity in rats based on molecular and biochemical parameters. Materials and Methods. The experiment was conducted on 56 outbred female rats that received oral administration of aluminum hydroxide at a dose of 15 mg/kg and a chelate complex of oxidized pectin with oxymethyluracil (50 mg/kg) under various preventive and post-exposure regimens for 3-4 months. The expression of metallothionein genes (Mt1, Mt2, Mt3) and zinc transporter genes (Zip1, Zip8) in liver tissue was determined by real-time PCR using specific primers, SYBR Green intercalating dye, and the reference gene Gapdh. Serum activity of AST, ALT, ALP, and LDH was measured; statistical analysis was performed using IBM SPSS Statistics 21 software with one-way ANOVA at a critical significance level of p=0,05. Results. In our study, chronic aluminum exposure was associated with an increase in Zip1 gene expression in the liver, whereas continuous administration of the oxidized pectin-oxymethyluracil complex normalized its expression to control levels. The expression of Zip8 and metallothionein genes (Mt1a, Mt2a, Mt3a) did not change significantly among the experimental groups. At the biochemical level, this complex, when used preventively, contributed to a reduction in AST and LDH activity. Conclusion. The oxidized pectin-oxymethyluracil complex in a rat model of chronic aluminum hydroxide exposure normalizes Zip1 gene expression and reduces AST and LDH activity. Further studies using an expanded set of morphological and molecular markers are required to clarify the organoprotective mechanisms of the complex.

Introduction. Transposons are DNA sequences capable of moving through the genome. LINE1 is the only autonomous transposon that is still actively replicated in humans, thus playing a key role in the evolution and regulation of the genome. The experts have observed increased mobility of LINE1 as a result of exposure to certain known carcinogens, such as heavy metals, benz(a)pyrene and bisphenol A.The study aims to research the expression level of LINE1 transposons in the kidneys and liver of model animals exposed to chronic exposure to various doses of cadmium chloride.Materials and methods. Five groups of Wistar rats (72 in total, 7 males and 7 females in the experimental groups and 8 males and 8 females in control group) were formed for the experiment. Experimental groups received a cadmium chloride solution in water at doses of 0.001, 0.01, 0.1, and 1 mg/kg.Results. The authors observed a dose-dependent increase in the level of LINE1 transcription, but statistical analysis did not show a significant increase in the level of relative transposon expression. The evaluation of the variances revealed significant differences from the control group in animals exposed to high doses of the toxicant. There are weak associations between the levels of relative expression of metallotineins and transposon genes.Limitations. The study was conducted on rats, and its results cannot be automatically transferred to humans. The obtained levels of relative transposon expression are highly susceptible to random fluctuations, which, together with the small size of the studied sample, necessitates further research on a larger sample in order to obtain more reliable results.Conclusion. The results obtained suggest the presence of cadmium-induced activation of transposon LINE1 transcription in rat organs, but the result did not reach the level of statistical significance. At the same time, the increase in variance in the experimental groups suggests that activation depends on a variety of factors mediating the response to toxic effects.Ethics. The study was approved by the bioethical Commission of the Ufa Research Institute of Occupational Health and Human Ecology on 11.12.2023 No. 01-12. Throughout the study, the animals were kept in standard conditions with twelve hours of artificial light during the daytime, a relatively constant humidity level (30–70%) and an air temperature of plus 20–25°C. Manipulations with all animals were carried out strictly in compliance with the rules set out 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 Humane Treatment of Animals.Contributions:Karimov D.D. — research concept and design, PCR, material collection and processing, statistical data processing, text writing, editing;Mukhammadieva G.F. — RNA isolation, PCR, material collection, editing;Ryabova Yu.V. — concept and design of research, organization of experiment, collection of material;Repina E.F. — concept and design of research, collection and processing of material;Gizatullina A.A. — conducting PCR, collecting material, editing;Smolyankin D.A. — conducting experiments on animals, collecting material;Karimov D.O. — research concept and design, experimental organization, statistical data processing, editing.Funding. Industry research program of the Federal Service for Supervision of Consumer Rights Protection and Human Well‑being for 2021-2025, p. 6.1.9 "Experimental substantiation of highly sensitive markers of toxic metal exposure to the body and development of preventive measures".Conflict of interest. The authors declare no conflict of interest.Received: 29.12.2025 / Accepted: 28.04.2026 / Published: 02.06.2026

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

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

Introduction. Among the means currently used for water disinfection, hydrogen peroxide is characterised by high efficiency, environmental friendliness, and safety. However, due to extremely low established MPC values (0.1 mg/L) it is not widely used.Objective. Investigation of the chronic effects of hydrogen peroxide on the body in white rats for determination of the no-observed concentration by toxicological signs of damage.Materials and Methods. White outbred rats were injected with hydrogen peroxide solutions for six months 5 times a week in doses of 50 mg/kg, 5 mg/kg, 0.5 mg/kg and 0.05 mg/kg. In animals, after 1, 3, and 6 months of exposure and after the recovery period, the functions of the nervous system, liver, and kidneys were evaluated, and the peripheral blood composition was recorded. A macroscopic pathomorphological examination of the internal organs was performed. The expression of GSTT1 and GSTM1 genes related to glutathione metabolism, was determined.Results. After 6 months, a decrease in lactate dehydrogenase, creatine phosphokinase, and hemoglobin levels was recorded in the blood serum in rats at the maximum tested dose. The study of lipid metabolism showed a decrease in the level of low-density lipoproteins and phospholipids when exposed to hydrogen peroxide at doses of 50 and 5 mg/kg. Suppression of GSTT1 gene expression was noted, and a high level of GSTM1 gene expression was observed in the group receiving a dose of 50 mg/kg of hydrogen peroxide.Limitations. The work was carried out only on laboratory animals.Conclusion. The most informative markers of chronic toxicity of hydrogen peroxide were the cumulative indices of lipid metabolism, as well as the degree of expression of the GSTM1 and GSTT1 genes of the antioxidant defense system, reflecting the severity of oxidative stress. Based on the data obtained, the dose of 5 mg/kg/day can be regarded as a threshold. The estimated maximum inactive concentration of hydrogen peroxide in water, equal to 35 mg/L, can serve as a guideline for adjusting sanitary and hygienic standards related to disinfection of pool water.Compliance with ethical standards. The Ethics Commission of the Federal Research Institute for Disinfectology has approved a research program of сhronic effects of hydrogen peroxide on rats (Minutes of the meeting No. 7 of October 21, 2024).Contribution: Bidevkina M.V. – concept and design of the study, editing, approval of the final version of the article, responsibility for the integrity of all parts of the article; Vinogradova A.I. – statistical processing; Morozov A.S. – concept and design of the study, collection and processing of material, writing text; Matrosenko M.V. – statistical processing;Pankratova G.P. – concept and design of the study; Latipova R.I. – statistical processing; Shaykhutdinova Z.K. – concept and design of the study, collection and processing of material, statistical processing, writing text; Karimov D.O. – conducting genetic research, processing results; Valova Ya.V. – preparation of equipment, validation of the method for assessing the content of hydrogen peroxide, sample preparation of biomaterial; Gizatullina A.A. – preparation for experiments; Sinitskaya T.A. – general idea and scientific supervision; Safandeev V.V. – editing. All authors are responsible for the integrity of all parts of the manuscript and approval of the manuscript final versionConflict of interest. The authors declare no conflict of interest.Funding. The study had no sponsorship.Received: June 02, 2025 / Received after revision: July 02, 2025 / Accepted: September 19, 2025 / Published: October 20, 2025

The effects of the combined exposure to food preservatives and chronic stress on the liver remain poorly understood, although both factors are widespread in the modern world. Objective. The aim of the study is to determine the nature and degree of morphological changes in rat liver after 28-day exposure to sorbic and benzoic acids and to find out whether chronic psychological stress enhances the toxic effect of the above-mentioned food preservatives. Materials and Methods. The authors conducted a 28-day in vivo experiment. Male rats (n=24) were divided into 4 equal groups: control, chronic stress, food preservatives, and combined effect of the above-mentioned factors. After euthanasia, histological examination and morphometry were performed. We assessed the area of hepatocyte nucleus and cytoplasm, the nuclear-cytoplasmic ratio (NCR), and the number of binucleated and anucleate cells. Statistical analysis was performed using the bootstrap method with Holm-Bonferroni correction (p<0.05). Results. Chronic stress decreased the nuclear area (-20 %, p<0.0001) and the cytoplasm area (-16 %, p<0.0001), but increased the number of binucleated hepatocytes (+71 %, p=0.006). Necrotic changes were not recorded. Preservatives caused moderate hepatocyte hypertrophy (nuclear area +11 %, p=0.0004) without increase in NCR and cytolysis. Under the collective effect of factors, the cytoplasm area decreased (-10 %, p=0.0060), and NCR increased (+18 %, p=0.0005) with preserved architecture and an unchanged number of binucleated cells. Conclusion. Chronic stress modifies early hepatotoxic effects of sorbic and benzoic acids. The process is accompanied by an increase in the nuclear-cytoplasmic ratio. Final conclusions on the problem under consideration require further development of mathematical approaches to the analysis of the toxic effect of a chemical agent under chronic psycho-emotional stress.