Yana Valeryevna Valova

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. 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. 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

Malignant neoplasms of the reproductive system are the leading cause of cancer mortality among women. Vascular endothelial growth factor (VEGF) is one of the most important factors in the malignancy process, but association of its gene polymorphisms with the risk of developing reproductive organ cancers remain contradictory. Polymorphisms in the VEGFA gene promoter region (rs2010963, rs699947) are functionally significant and associated with increased protein expression, which enhances angiogenesis. The rs3025039, located in the 3'-UTR, influences post-transcriptional regulation of the gene. The aim of the study was to compare the association of rs2010963, rs699947 and rs3025039 polymorphisms of the VEGFA gene with the risk of developing malignant neoplasms of the female reproductive system using a meta-analysis method. Materials and Methods . A systematic literature search of domestic and international databases identified 15 case-control studies. Statistical analysis was performed using a random-effects model. Results. A significant increase in the risk of female reproductive system cancers was associated with the minor alleles of VEGFA polymorphisms rs2010963 (OR = 1.24; 95% CI: 1.09–1.41; p = 0.0008) and rs699947 (OR = 1.16; 95% CI: 1.04–1.28; p = 0.0058). No such association was identified for rs3025039. The analysis indicated substantial heterogeneity among the included studies. Conclusion. The results of the meta-analysis confirm the role of VEGFA gene polymorphisms in modulating the risk of female reproductive system cancer and indicate the need to consider ethnic and nosological characteristics in further research.

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

Ovarian cancer remains one of the most common causes of death from gynecological cancer in women worldwide. Its course depends on many factors, including genetic and epigenetic disorders. MicroRNAs are currently considered one of the most promising prognostic and diagnostic markers for solid tumors. The aim of the study was to analyze the association of polymorphic loci of the microRNA-27a rs895819 and microRNA-146a rs2910164 genes with the risk of developing ovarian cancer.Material and Methods. Genotyping was performed by determining single nucleotide polymorphisms using the KASP method. For pairwise comparison of the frequency of occurrence of genotypes and alleles in patients with ovarian cancer and in the control group, the χ2 test was used for 2×2 contingency tables. If there are statistically significant differences between the compared samples, the odds ratio (OR) and the boundaries of the 95 % confidence interval (95 % CI) were assessed. Quantitative characteristics were compared using the Mann – Whitney test (in the case of two groups) and the Kruskal – Wallis test (in the case of three groups).Results. As a result of a comparative analysis of the distribution of frequencies of alleles and genotypes of the polymorphic locus rs2910164 of the miR-146a gene in a sample of patients with ovarian cancer and healthy individuals, it was shown that carriage of the homozygous genotype GG and allele G is a risk factor for women of Tatar ethnicity. No significant differences were detected in the distribution of allele frequencies and genotypes of the rs895819 polymorphic locus of the miR-27a gene.Conclusions. The polymorphic locus of microRNA-146a rs2910164 is associated with an increased risk of ovarian cancer in women of Tatar ethnicity.

Introduction. Vibration disease (VD) remains one of the most common occupational pathologies. Identification of molecular genetic markers associated with the development of VD is important for both improving the methodology of assessing occupational risks and developing personalized approaches to diagnosis, treatment, and prevention of the disease. However, there is a lack of information on the contribution of genetic aspects to the development of VD. In this work, there was made an assessment of the presence of associations between HTR1B, ADRA2A gene polymorphisms and the risk of VD development. The aim of the study is to assess the presence of associations between polymorphisms of the HTR1B and ADRA2A genes and the risk of developing VD. Materials and methods. The study involved eighty VD patients. The control group consisted of 103 cases without contact with vibration. Polymorphisms rs6298 of the HTR1B gene and rs7090046 of the ADRA2A gene were analyzed by polymerase chain reaction using specific oligonucleotide primers and locus-specific DNA probes in real time. Results. Despite certain trends in the distribution of genotype and allele frequencies of the polymorphic loci rs6298 of the HTR1B gene and rs7090046 of the ADRA2A gene, statistically significant differences between VD patients and the control group were not found. Limitations. Limitations of this study include the small sample size and the analysis of only one polymorphism of each of the two genes (HTR1B and ADRA2A). Conclusion. Based on the obtained data, it can be assumed that the polymorphic loci rs6298 of the HTR1B gene and rs7090046 of the ADRA2A gene cannot serve as reliable markers of predisposition to VD in the studied sample. However, continuation of the study in larger samples and taking into account other genetic factors may be useful for a deeper understanding of the molecular mechanisms involved in the pathogenesis of VD.

Aluminum is one of the most abundant elements in the Earth’s crust and is widely used in industry, domestic applications, and medicine. Despite its extensive utilization, its potential toxicity remains a subject of active scientific debate and investigation. The main routes of aluminum entry into the human body include food, drinking water, inhaled air, and pharmaceutical products, all of which contribute to its accumulation in biological tissues and increase the risk of chronic intoxication. Vulnerable populations include children and individuals with impaired renal function, particularly those with chronic kidney disease. The aim of this study was to evaluate the effects of chronic exposure to aluminum hydroxide on kidney morphology and the expression of Mt1a, Mt2a, and Mt3a genes in rats, with an emphasis on identifying dose-dependent effects and elucidating possible mechanisms of nephrotoxicity. The experiment was conducted on 40 female white rats randomly assigned to one control and four experimental groups (8 animals each). Over the course of four months, the experimental groups received aluminum hydroxide orally in varying doses. Toxicity assessment included quantitative real-time PCR analysis of gene expression and histological examination of renal tissue. Significant upregulation of Mt2a and Mt3a was observed at higher aluminum doses (p < 0.001), while Mt1a expression demonstrated high interindividual variability. Histopathological evaluation revealed signs of interstitial inflammation, fibrosis, and chronic glomerulonephritis. Chronic exposure to aluminum hydroxide induces pronounced dosedependent morphological and molecular changes in the kidney. The Mt2a and Mt3a genes may serve as promising molecular biomarkers of aluminum-associated nephrotoxicity.

Evaluation of rat behavior in experimental studies is important for understanding neurophysiological and psychopharmacological processes. The aim of this study is to investigate the effect of paracetamol on the behavioral responses of laboratory rats under chronic stress. Four groups of white outbred rats (N=48) were formed within the framework of the study. For statistical analysis of the data, specialized IBM SPSS Statistics version 21 software was used. The normality of distribution was checked using the Kolmogorov-Smirnov criterion. The data were then evaluated using one-way analysis of variance (ANOVA), with Tukey and Tamhane criteria used for multiple comparisons. The focus is on assessing changes in the cognitive and emotional spheres of animal behavior, as well as analyzing the possible neuroprotective properties of paracetamol under long-term stress exposure. This article describes changes in the behavioral responses of animals from different groups to objectively assess the effect of the drug on the levels of anxiety, depression, aggression and cognitive functions in rats under chronic stress. The behavior of rats on a board with holes, in a cage for measuring activity, in the Open Field and Elevated Plus Maze tests during a four-week study against the background of taking an aqueous solution of paracetamol is described. The results of this study confirm the hypothesis that the combination of stress and paracetamol intake has a significant effect on the behavioral activity of laboratory rats. This is manifested in a decrease in vertical and horizontal activity, changes in behavior in the elevated plus maze and a decrease in mobility in the open field. The obtained data can serve as a basis for further studies of the mechanisms of interaction between stress and pharmacological drugs on the central nervous system of animals.

Introduction. Microparticles of plastic (MP) pose a threat to health, but the processes of their accumulation and distribution in living organisms, especially in brain tissues, have not been sufficiently studied. The aim of the study was to compare the accumulation of plastic microparticles of different sizes (100, 500 and 1000 nm) in the brain of rats using a descriptive and quantitative approach. Material and methods. Female Wistar rats, 12 individuals divided into 4 groups, were intracardiacally injected with a suspension of fluorescent polystyrene microparticles (100, 500 and 1000 nm in diameter) or a saline solution (Control) with a volume of 50 µl. The accumulation of microplastics in brain tissues was assessed using fluorescence microscopy using a descriptive approach and a computer program for quantifying the content of microparticles and their conglomerates. The data was analyzed using the Bootstrap method with the Holm–Bonferroni correction, the significance of the differences was determined at p < 0.05. Results. It was found that fluorescent microparticles of plastic accumulate mainly in the cerebral cortex, and the MP 1000 group showed a greater number of clearly defined conglomerates compared to the MP 100 and MP 500 groups. The density of plastic microparticles, estimated using an automated morphometric approach, was also higher in the experimental groups compared with the control, especially in the MP 1000 group. Limitations. The study was limited to studying the distribution of plastic microparticles of three sizes in a toxicological experiment on a single animal species (laboratory rat). The phase of the sexual cycle of female rats was not taken into account. Conclusion. The integration of approaches allows for a deeper understanding of the dynamics of microparticle accumulation: a descriptive approach shows the ability of particles to penetrate the blood–brain barrier (BBB), while a quantitative approach provides data on the content and distribution of particles and conglomerates.