Introduction. It is known that the antitumor drug doxorubicin (Dox) is a reprotoxicant that has a negative effect on reproductive function in mammals. In the male body, doxorubicin leads to significant damage to testicular cells, inducing DNA damage, the formation of double-stranded breaks, crosslinking, and free radicals.

The purpose of this work was to examine the effect of doxorubicin on the development of spermatogenic epithelial cells in vitro.

Material and methods. The study was performed on the primary culture of mouse spermatogenic epithelium. The cytotoxic effect of doxorubicin was studied at concentrations of 0.25, 0.05, and 0.005 µg/ml. The degree of cytotoxicity and viability of cells was assessed by their morphological state, DNA damage, and the dynamics of the number of living cells in culture for 40 days.

Results. 24 hours after exposure to Dox, a dose-dependent statistically significant decrease in cell viability was observed in all the studied samples, with the maximum effect – a decrease in the number of live cells to 50% – observed at a concentration of 0.25 µg/ml, and a decrease to 13% at a concentration of 0.05 µg/ml. The decrease in cell viability persisted in subsequent stages of cultivation, which determined the nature of the monolayer, as well as changes in the morphology of the Sertoli cells.

Limitations. The obtained results refer to a heterogeneous cell culture as the object of research.

Conclusion. During the experimental work, all the studied concentrations of doxorubicin showed a cytotoxic effect on somatic and spermatogenic cells. The most harmful concentrations of doxorubicin for spermatogenic epithelial cells in vitro were 0.25 and 0.05, which led to the cell death within 24 hours and caused DNA damage after four hours of exposure. The study revealed characteristic features of pathomorphological changes in Sertoli cells. Even at low concentrations, doxorubicin can disrupt the formation of the feeder layer.

Compliance with ethical standards. The study was approved by the Bioethics Commission of the Research Institute of General Prophylaxis and Epidemiology of the Federal Medical and Biological Agency of Russia (Minutes No. 2 dated March 28, 2023).The animals were removed from the experiment in accordance with GOST 33215-2014 and in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123), Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contribution:
Golubentseva Yu.V. – study concept and design, data collection and processing, statistical analysis, text writing;
Popov V.B. – text writing, editing;
Radilov A.S. – writing and editing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all parts of the article.

Conflict of interest. The authors declare that they have no apparent or potential conflicts of interest related to the publication of this article.

Funding. The study had no sponsorship.

Received: 28 апреля 2026 /Revised: 12 мая 2026 / Accepted: / Published: 2026

Introduction. The search for new effective and safe hepatoprotectors is an urgent task in experimental toxicology and pharmacology. Natural polyphenols, particularly the isoflavone genistein, are considered promising compounds due to their antioxidant and anti-apoptotic properties.

The aim of this study is to experimentally evaluate the hepatoprotective efficacy of genistein in a model of acute toxic hepatitis induced by carbon tetrachloride (CCl₄).

Material and methods. The study was performed on 84 male white non-pedigree rats. Acute toxic hepatitis was simulated by a single intragastric administration of carbon tetrachloride (CCl₄) at a dose of 1 ml/kg. The hepatoprotective effect of genistein was studied by a single intragastric administration at a dose of 150 mg/kg 2 hours before CCl₄. Silymarin was used as a reference drug, which was also administered intragastrically at a dose of 150 mg/kg 2 hours before CCl₄. The animals were divided into four groups: biological control, CCl₄ administration, silymarin + CCl₄ administration, and genistein + CCl₄ administration. The effectiveness was assessed based on survival rates, body weight dynamics, liver weight, the propofol test, and the activity of ALT, AST, and alkaline phosphatase (ALP) in the blood serum. Statistical processing of the obtained data was performed using the GraphPad Prism 10 software. The statistical significance of differences in survival rates was assessed using the χ² test, and the Mann-Whitney U-test was used to assess quantitative indicators.

Results. CCl₄ administration led to the death of 13% of the animals, while silymarin reduced the mortality rate to 9%, while genistein provided 100% survival rate. Genistein statistically significantly reduced the activity of ALT on the 1^st and 3^rd days compared to the CCl₄ group and demonstrated better efficacy compared to silymarin in correcting cholestasis (reduction of ALP) and restoring the liver’s detoxification function (propofol test).

Limitations. The limitations of the study are due to the fact that the results were obtained in experiments on rats, which does not allow for direct extrapolation to humans. The work did not carry out a morphological assessment of the liver, any parameters of oxidative stress, inflammation, serum bilirubin and albumin, GGT activity or other additional markers of liver damage were not determined, which limits the completeness of the characteristics of the hepatoprotective effect of genistein.

Conclusion. Genistein has a hepatoprotective effect, exhibits a more pronounced effect compared to silymarin in a number of studied parameters and can be considered as a promising compound for further study in hepatology.

Compliance with ethical standards. The experimental study was approved by the local bioethics committee of the Center for Experimental Pharmacology at SPbSU (protocol No. Rats–01–FD-25 dated 06.10.25 and No. Rats–01–FD-26 dated 11.11.25).

Contribution of the authors:
Erlin G.V. – conducting the experiment; statistical processing and analysis of the results, writing text;
Karavaeva A.V. – biochemical analysis of rat serum samples;
Strelova O.Yu. – material analysis, editing;
Grebenyuk A.N. – the concept and design of the study; material analysis, editing.
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 the absence of obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: April 23, 2026 / Revised: April 25, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

Introduction. Long-term health risks increase due to occupational and environmental exposure to lead compounds, one of the main targets of which is the mitochondria at the subcellular level. Lead inhibits the activity of energy metabolism enzymes, including succinate dehydrogenase (SDH). Currently, the data on sex-related physiological and metabolic differences that may influence these toxic effects are limited.

The aim of the study was to experimentally determine the nature of the effect of lead acetate on SDH activity in peripheral blood lymphocytes of rats, depending on sex.

Material and methods. The experiment was performed on outbred male and female rats (3–4 months old, body weight 220 ± 20 g). The animals were divided into 4 groups (n = 10): “Lead ♀” and “Lead ♂” received lead acetate with water (819 mg/l) for 45 days, “Control ♀” and “Control ♂” received drinking water. After exposure, the area of formazan levels was determined in blood smears using BloodRunner and BioImagine software to assess SDH activity, for which the samples were incubated in appropriate solutions containing oxidized nitrosinium tetrazolium and SDH substrate succinate. Statistical processing was performed using Python (version 3.11), SciPy (version 1.11.1) and statsmodels (0.14.0) libraries. In the two-factor assay, rank analysis of variance was applied, and the Mann–Whitney U-test with the Bonferroni correction (p < 0.05) was used for pairwise comparisons.

Results. Statistically significant effects of the factors “lead” and “sex” and their interaction were revealed. In lead-exposed females the activity of SDH did not change compared to the control (p = 0.270), while in lead-exposed males the activity of SDH significantly decreased (p < 0.001). The difference between the groups “Lead ♀” and “Lead ♂” also had high significance (p < 0.001).

Limitations. Only one parameter, SDH activity, was evaluated. In this study, we limited ourselves to assessing the total SDH activity, as preliminary experiments showed that the contribution of endogenous succinate was insignificant in our conditions and did not affect the comparative results of the groups.

Conclusion. Lead acetate inhibits SDH in blood lymphocytes in a sex-specific manner: male rats are more sensitive than female rats. It is necessary to take sex into account when assessing the health risks associated with lead contamination.

Compliance with ethical standards. The experiment was approved by the Local Ethics Committee of the Yekaterinburg Medical and Scientific Center for Prevention and Health Protection of Industrial Workers, Rospotrebnadzor (Protocol No. 1A dated 03.02.2025) in accordance with the European Convention for the Protection of Vertebrate Animals Used for Experimental and Other Scientific Purposes (ETS N 123), and Directive 2010/63/EC of the European Parliament and of the Council of 22 September 2010 on the Protection of Animals Used for Scientific Purposes.

Authors’ contribution. All co-authors made an equal contribution to the research and preparation of the article for publication, and all co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interests. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: March 6, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

The search for new highly analgesic agents devoid of the side effects characteristic of the µ-opioid receptors agonists (drug dependence, respiratory depression, gastrointestinal disorders) is one of the priorities in the development of modern medicine. In this regard, selective k-opioid receptor agonists are of considerable interest, as they exhibit a pronounced analgesic effect comparable to that of µ-opioid receptor agonists. However, their widespread introduction into medical practice is limited by a high risk of affective disorders. In addition, the lack of a unified methodological approach to the assessing of side effects of k-opioid receptor agonists at the preclinical study stage leads to fragmented data and makes it difficult to form a reliable system for predicting their therapeutic potential and safety profile.

The material for the analysis was the literature sources presented in the bibliographic databases PubMed, Scopus, Web of Science, MedLine, RSCI and eLIBRARY.RU.

The article discusses the results of domestic and foreign studies on methods for evaluating and interpreting the effects of compounds with k-opioid activity. The necessity of applying a comprehensive approach is demonstrated, including molecular and cellular modeling methods, studies on isolated tissues, preclinical investigations, and strictly regulated clinical trials. A flowchart reflecting the structure of the experimental study of the mechanism of action and pharmacological effects of k-opioid receptor agonists has been developed.

The systematization of study strategies will improve the accuracy of assessing the therapeutic activity, tolerability and safety of compounds of this class, which will help to increase the prognostic significance of the data obtained, as well as reduce the complexity and duration of research.

Author contribution:
Subbotina S.N. – the concept and design of the study, collection of material and data processing, text writing and editing;
Shcherbinina K.E. – collection of material and data processing, text writing and editing;
Nikiforov A.S. – editing, critical revision of the manuscript;
Yudin M.A. – editing, approval of the final version of the article.
All co-authors – responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no sponsorship.

Received: November 25, 2025 / Revised: February 25, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

Introduction. Cytostatic drugs are widely used in oncology practice; however, their handling is associated with occupational and environmental exposure risks. In the Russian Federation, requirements for the management of medical waste generated during the use of cytostatic and other hazardous medicinal products are established by Federal Laws No. 52-FZ “On the Sanitary and Epidemiological Welfare of the Population”, No. 89-FZ “On Production and Consumption Waste”, and No. 323-FZ “On the Fundamentals of Public Health Protection in the Russian Federation”, as well as by Sanitary Rules SanPiN 2.1.3684–21, which regulate sanitary and epidemiological requirements for waste management and provide for the need for its decontamination.

At the same time, the current regulatory and methodological documents of the Russian Federation mainly regulate the organizational, sanitary and epidemiological aspects of handling such waste, but do not contain scientifically justified criteria for selecting deactivation methods and/or clear instructions depending on the chemical nature of the substances and their transformation products. This creates certain difficulties for practical services, control and supervisory authorities in implementing the provisions of the sanitary legislation of the Russian Federation.

The purpose of the study was to summarize data on current approaches to the deactivation of cytostatic drugs, taking into account the assessment of their effectiveness, limitations, and the completeness of chemical-analytical and toxicological evidence confirming the absence of hazardous properties after degradation.

Materials and methods. A review of scientific publications, regulatory and methodological documents, international guidelines on the handling of hazardous medicinal products, and materials indexed in the open scientific databases PubMed, Scopus, Web of Science, eLIBRARY.RU, RSCI and CyberLeninka was conducted. The analysis took into account the chemical nature of the drug, the deactivation method, the degree of degradation of the parent compound, data on the identification of transformation products, mineralization parameters, and the results of mutagenicity, cytotoxicity and ecotoxicity assessments.

Results. Cytostatic drugs represent a toxicologically significant group of drugs; some of their representatives adversely affect the endocrine system in humans and animals and are classified by the expert community as carcinogens, mutagens and reproductive toxicants of hazard category 1. At the same time, both Russian and international regulatory and methodological documents contain substantial gaps regarding their deactivation.

Current approaches include oxidative, photochemical, photocatalytic and electrochemical methods, as well as complexation. The choice of an appropriate method is determined by the chemical structure of the parent compound, the composition of the matrix, treatment conditions and the properties of the resulting transformation products.

Assessment of the effectiveness of an approach to the deactivation of medicinal products should include the following stages: selection of an appropriate degradation method, chemical-analytical assessment of the degree of parent compound degradation and identification of transformation products, assessment of mineralization degree, evaluation of the toxicity of degradation products, and interpretation of the results obtained.

Limitations. The study was limited to the analysis of open literature, regulatory, methodological and guidance sources. Closed industrial data, unpublished reports and original experimental verification of the effectiveness of deactivation methods were not included. Data comparability was limited by differences in matrix composition, cytostatic drug concentrations, treatment conditions and the completeness of chemical and toxicological assessment of transformation products.

Conclusion. Taking into account the widespread use of cytostatic drugs in medical practice, as well as their toxicity and hazard, including when present in waste, it appears appropriate to develop and incorporate into the regulatory and methodological framework of the Russian Federation documents, including methodological guidelines and guidance documents, that contain criteria for selecting appropriate deactivation methods, as well as lists of recommended methods, procedures and reagents.

Authors’ contribution:
Khamidulina Kh.Kh.,Tarasova E.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;
Kurpedinov K.S., Nazarenko A.K. – collecting and processing material, writing text, editing.

Conflict of interest. The authors declare no apparent and potential conflicts of interest in relation to the publication of this article.

Funding. The study had no sponsorship.

Received: March 20, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

Introduction. In preventive toxicology, the problem of the possible development of long-term effects in humans upon contact with various chemicals is one of the most significant. Since male personnel is predominantly involved in the production, storage and use of chemicals of varying degrees of toxicity, special attention should be paid to studying the effect of these compounds on male sexual function when developing measures to prevent long-term consequences. However, the gonadotoxic properties of unsymmetrical dimethylhydrazine (a component of rocket fuel) have not been studied in detail in the context of its long-term oral exposure.

The aim of the study was to experimentally evaluate the effects of chronic intragastric exposure of unsymmetrical dimethylhydrazine on male reproductive function with the establishment of threshold and maximum inactive doses.

Material and methods. The object of the study was unsymmetrical dimethylhydrazine (heptyl, 1,1-dimethylhydrazine (CH₃)₂N₂H₂, CAS No. 57-14-7) with a mass fraction of 99% and a specific density of d₄²⁰ = 0.7914 g/cm³. Heptyl in the form of aqueous solutions was orally administered daily for six months to male rats of three experimental groups (10 rats per group) in the following doses: 4·10^–⁴ mg/kg – 1^st experimental group; 8·10^–⁵ mg/kg – 2^nd experimental group and 1.5·10^–⁵ mg/kg – 3^rd experimental group. After the specified period, the spermogram, spermatogenesis and reproductive capacity of the males in each group were evaluated and fetal material was analyzed for the presence of developmental abnormalities.

Results. It was found that chronic intragastric administration of heptyl to white non-linear rats at the specified doses did not reduce the male rats’ ability to mate and fertilize, did not affect the spermogram parameters, and did not cause any teratogenic effects in the offspring. However, long-term exposure to the compound at the maximum dose significantly reduced the number of spermatogonia and the number of layers of spermatogenic epithelium in the testes of the experimental rats. Additionally, the offspring of the male rats in this group showed signs of embryotoxicity, which manifested as a decrease in cranio-caudal size.

Limitations. The experimental study of chronic oral exposure of heptyl on male reproductive function does not provide an assessment of other long-term effects.

Conclusion. Based on the complex of changes detected, the threshold dose of chronic intragastric exposure to unsymmetrical dimethylhydrazine on the reproductive function of male rats was recognized as 4.0·10^-⁴ mg/kg, and the maximum inactive dose – 8.0·10^-⁵ mg/kg. The identified features of the negative impact of unsymmetrical dimethylhydrazine were taken into account when justifying its MPC in water bodies.

Compliance with ethical standards. The experimental study was approved by the Research Institute of Hygiene, Toxicology and Occupational Pathology» of the FMBA of Russia (Protocol No. 5 of December 10, 2024) and conducted in accordance with the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (ETS No. 123), Directive of the European Parliament and of the Council of the European Union 2010/63/ EU of 22.09.2010 On the Protection of Animals Used for Scientific Purposes.

Authors’ contribution.
Maslennikov A.A. – study concept and design, analysis of the results, text writing;
Shateeva A.V. – research planning and execution;
Novikova O.N. – editing.
All co-authors – approval of the final version of the article, responsibility for the integrity of all parts of the article.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study was conducted within the framework of the state program of the Russian Federation «Scientific and Technological Development of the Russian Federation».

Received: March 3, 2026 / Revised: May 4, 2026 /Accepted: June 1, 2026 / Published: June 30, 2026

The article considers the implementation of the concept of an interdisciplinary (multidisciplinary) approach at all stages of providing emergency medical care to patients with acute poisoning using multimodal technologies in the diagnosis, treatment and rehabilitation of toxic lesions. It is noted that clinical toxicology is closely related to a number of fundamental medical sciences, and the share of advisory assistance from related specialists in the structure of medical services for this pathology is high. Using the example of a multidisciplinary emergency hospital, the key role of interdisciplinary interaction is demonstrated.

The work is based on the analysis of data from international (Scopus, Web of Science, PubMed) and Russian (RSCI, eLibrary.RU, CyberLeninka) scientific databases.

The systematic introduction of interdisciplinary interaction into clinical practice is a prerequisite for improving the effectiveness and quality of medical care in acute poisoning.

Authors’ contribution:
Antonova A.M. – concept and design of research, collection and processing of material, writing, editing;
Lodyagin A.N., Barsukova I.M., Batotsyrenov B.V. – concept and design of research, writing, editing;
Narzikulov R.A., Sinenchenko A.G. – writing, editing;
Kuznetsov S.V., Shikalova I.A. – collecting and processing of material, writing text, editing.
All co-authors are responsible for approving the final version of the article and ensuring the integrity of all its parts.

Conflict of interest. The authors declare that there are no obvious and potential conflicts of interest in connection with the publication of this article.

Funding. The study had no financial support

Received: February 6, 2026 / Revised: March 30, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026

Received: April 27, 2026 / Revised: May 22, 2026 / Accepted: June 1, 2026 / Published: June 30, 2026