No 2 (2024)

Introduction. The search for new highly effective medicines with a wide range of pharmacological effects and low toxicity is one of the priorities of the development of modern pharmacy and medicine. The development of medicines intended for the treatment of poisoning by chemical substances of hepatotoxic action remains actual. Substances of plant origin, in particular genistein, are of great interest in this regard.

Material and methods. The material for the analysis was the sources of literature, abstracting in the bibliographic databases of PubMed, Scopus, and RSCI.

Results. The article discusses the results of domestic and foreign studies devoted to the study of the biological effect of genistein. Its structure, toxicity and mechanisms of action are described. The results of studies confirming the effectiveness of genistein in protecting the liver, as well as in reducing the toxic effects on this organ in case of poisoning, are considered. A section is highlighted that examines the possibility of using genistein in various medical fields and its potential for the prevention and treatment of pathologies caused by hepatotoxicants.

Limitations. The review was prepared based on a study of 44 literature sources published over the period from 1998 to 2023, which represents a fairly representative sample.

Conclusion. Genistein, which has a pronounced antioxidant activity, can potentially be used to treat poisoning with chemicals, in the mechanism of toxic action of which oxidative stress plays an important role, primarily hepatotoxicants.

Аuthors сontribution:
Erlin G.V. — collection of material in bibliographic databases, material analysis, writing the text of the article;
Strelova O.Yu. — material analysis, text processing and editing;
Grebenyuk A.N. — the concept and design of the study, material analysis, text processing and 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 no conflict of interest.

Funding. The study had no sponsorship.

Received: December 27, 2023 / Accepted: March 10, 2024 / Published: April 27, 2024

Introduction. 2-Ethylhexanoic acid is widely used in various industries: in the production of plastics, paints, enamels, varnishes, as a preservative, corrosion inhibitor, wetting agent, in the production of low molecular weight aromatic and aliphatic esters.

In order to ensure the safety of workers engaged in the production of 2-ethylhexanoic acid in the Russian Federation, it became necessary to conduct research to substantiate the hygienic norms for the content of vapors and aerosols of the substance in the air of the working area.

In accordance with HNs 1.1.701, if a substance belongs to a homologous series, the representatives of which have an approved MAC value for the air of the working area, the maximum allowable concentration can be set based on a comparison of known toxicometric parameters. According to Sanitary rules and norms 1.2.3685-21, for substances similar in structure, physicochemical properties and biological effects — hexanoic and isohexanoic acids — the values of the maximum single allowable concentration in the air of the working area are set at the level of 5 mg/m³, vapor, hazard class 3. An analysis of international databases showed that 2-ethylhexanoic acid is regulated in the air of the working area in Belgium (TWA 5 mg/m³, vapor and aerosol mixture).

The purpose of the work is to substantiate the hygienic norms for 2-ethylhexanoic acid in the air of the working area in the Russian Federation.

Material and methods. The materials used were domestic and international databases, reports, research protocols, scientific articles and monographs containing information on the physicochemical and toxic properties of hexanoic, 2-ethylhexanoic, 4-methylpentanoic and 2-propylpentanoic acids. The research methodology consisted of a comparative analysis of toxicometric parameters of substances similar in structure, physicochemical properties and biological effects and calculation of safe concentrations of 2-ethylhexanoic acid in the air of the working area according to established NOAEL values.

Results and discussion. A comparative analysis of the toxicometric parameters of hexanoic, 2-ethylhexanoic, 4-methylpentanoic and 2-propylpentanoic acids was carried out. Substantiate for the value of the maximum allowable concentration of 2-ethylhexanoic acid in the air of the working area is based on: 1) NOAEL at the level of 180 mg/kg/day according to the general toxic effect established in studies on male mice when administered intragastrically for 92–93 days; 2) NOAEL at 100 mg/kg/day for developmental toxicity established in rat studies when administered intragastrically during days 6–15 of pregnancy. 3) MAC values for structurally similar analogues.

Limitations. The study is limited to the study of open literature sources describing the toxicological characteristics of 2-ethylhexanoic acid.

Conclusion. As a hygienic norms in the air of the working area for 2-ethylhexanoic acid, the maximum single allowable concentration is recommended at the level of 5 mg/m³, vapor + aerosol, hazard class 3. The recommended MAC value is provided by the analytical control method MM-25-23 “Measurement of the mass concentration of 2-ethylhexanoic acid in the air of the working area, the atmospheric air of urban and rural settlements by capillary gas chromatography with mass spectrometric detection”, developed by F.F. Erisman Federal Scientific Center of Hygiene, Rospotrebnadzor (the lower limit of determination in the air of the working area is 0,5 mg/m³; number in the Federal Information Fund for Ensuring the Uniformity of Measurements — FR.1.31.2023.47327).

Compliance with ethical standards. The study does not require the submission of a biomedical ethics committee opinion or other documents.

Author contribution:
Khamidulina Kh.Kh. — 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;
Tarasova E.V. — concept and design of the study, collection and processing of materials, text writing, editing;
Zamkova I.V. — collection and processing of materials, writing text;
Nazarenko A.K. – editing.

Conflict of interest. The authors declare no conflicts of interest.

Funding. The study had no financial support.

Received: February 05, 2024 / Accepted: March 10, 2024 / Published: April 27, 2024

Introduction. This article discusses the problem of the effect of As₂O₃ on mitochondrial respiration in two types of cell cultures. Despite the fact that much has been achieved in the study of oxidative stress induced by arsenic compounds in a living organism, a number of gaps remain in understanding the mechanisms of arsenic damage to mitochondria in cells of different morphological types. In this work, a comparative analysis of the parameters of mitochondrial respiration in epithelial cells and fibroblasts exposed to different doses of As₂O₃ is carried out.

The purpose: to study the effect of As₂O₃ on mitochondrial respiration of 2 types of cells using the extracellular flow method.

Material and methods. The experiment was carried out on 2 types of human cells: fibroblast and epithelial cells. The design included 2 stages: stage 1 — dose selection according to the MTT test and cytomorphometry, stage 2 — the effect of additives that suppress or stimulate mitochondrial respiration and determine its parameters in cells exposed to different concentrations of As₂O₃.

Results. Cultures of fibroblasts and bladder epithelium differ in oxygen demand and bioenergy potential as well as in sensitivity to arsenic exposure. The calculated Bioenergetic Health Index helped reveal a dose-dependent change in mitochondrial respiration with the greatest inhibition observed at the mean dose for the fibroblast culture and at the minimum dose for bladder epithelium. The maximum dose caused an increase in the Index close to that of the control cells in both tissue cultures.

Limitations. To assess the effect of As₂O₃ on cell cultures, estimates calculated from one measured parameter of the bioenergetic function (oxygen consumption rate) were used. When conducting research, it is necessary to take into account the energy capacity of different types of cells.

Conclusion. The response of individual links of the mitochondrial respiratory chain upon exposure to arsenic depends on the cell type and the acting dose. Critical changes in mitochondrial respiration in the culture of the bladder epithelium were obtained with exposure to the minimum dose, and in the culture of fibroblasts — to the average.

Compliance with ethical standards. The study does not require the presentation of the conclusion of the biomedical ethics committee and other documents.

Authors contribution:
Gribova Y.V. — concept and design of the study, collection and processing of material, statistical analysis, writing the text, editing;
Bushueva T.V. — concept and design of the study, analysis and interpretation of results, statistical analysis, writing the text, editing;
Karpova E.P. — collection and processing of material, writing the text;
Labzova A.K. — collection and processing of material, editing;
Sakhautdinova R.R. — editing;
Gurvich V.B. — concept and design of the study, editing;
Sutunkova M.P. — concept and design of the study, 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 no conflict of interest.

Funding. The study had no sponsorship.

Received: Jule 18, 2023 / Revised: November 11, 2023 / Accepted: March 10, 2024 / Published: April 27, 2024

Introduction. Unsymmetrical 1,1-dimethylhydrazine (UDMH), a highly toxic, carcinogenic substance of the 1st hazard class, is the main nitrogen-containing rocket fuel, but to date, in the Russian Federation and abroad, effective methods have not been developed for the quantitative determination of UDMH biomarkers in biological among workers in the rocket and space industry. The aim of the study is to develop a new highly sensitive method for biological monitoring of UDMH using the most sensitive exposure biomarker – pyridoxal dimethylhydrazone in human urine using high-performance liquid chromatography with tandem mass spectrometric detection (HPLC-MS/MS). Material and methods. measurement of mass concentrations of pyridoxal dimethylhydrazone in urine was performed by HPLC-MS/MS in reverse-phase HPLC mode with preliminary concentration by solid-phase extraction. To ensure the uniformity of measurements, a standard sample of pyridoxal dimethylhydrazone was synthesized domestically according to the previously described scheme [9]. Results. a method for measuring mass concentrations of pyridoxal dimethylhydrazone in urine in the range from 10 ng/ml to 1 μg/ml was developed, metrologically certified and entered into the Federal Register by HPLC-MS with solid-phase extraction. Limitations of the study. ensuring the lower limit of quantification is achieved only through the use of a tandem mass selective detector. When using single quadrupole detectors, the limit increases by an order of magnitude. Conclusion. it is advisable to carry out biological monitoring of the industrial effects of UDMH on the body of people in contact with it based on the quantitative determination of pyridoxal dimethylhydrazone in urine using the HPLC-MS method. The developed method makes it possible to measure the mass concentrations of pyridoxal dimethylhydrazone in urine in the range from 10 ng/ml to 1 μg/ml, which, according to estimates, will reveal the intake of 210 μg of UDMH per person weighing 70 kg per shift, corresponding to an 8-hour exposure to concentration 21 µg/m3 or 1/5 TWA (0.1 mg/m3).

Introduction. Currently existing antiplatelet agents exhibit a wide range of side effects that limit their use. It is urgent to search for and create an effective agent for the correction of increased thrombogenic potential and having a wide profile of drug safety. This article presents the results of a toxicological study of a new benzimidazole derivative of the compound RU-891, which exhibits pronounced antiplatelet properties. Material and methods. Groups of control and experimental animals – nonlinear rats of both sexes – were formed to conduct research. The introduction of the tested PS (pharmaceutical substance) on a solution of distilled water in a volume of 4 ml/kg was carried out intragastrically, daily for 6 months. The studied PS RU-891 was administered to rats in doses: 23 mg/kg – 1st experimental group; 460 mg/kg – 2nd experimental group. The control group of animals was intragastrically injected with distilled water at a dose of 4 ml/kg. During the experiment, weekly measurements of body weight were carried out, body weight was expressed in g, an increase in %. Behavioral activity was studied in the classic “open field” test at the end of the 1st, 6th and 7th months of the chronic experiment. The study of the state of the cardiovascular system was carried out by electrocardiography recorded in anesthetized animals. The assessment of the excretory function of the liver and the excretory function of the kidneys was carried out using stress tests with the dyes “bromosulfalein” and “phenolic red”. The effect of PS RU-891 on the hematological parameters of the peripheral blood of rats was assessed according to the following indicators: the total number of erythrocytes, platelets, hemoglobin levels, hematocrit, and the number of leukocytes. The classic Mas-Magro test was used to assess the effect on blood clotting. During morphological examination, a macro- and microscopic assessment of the state of organs was performed and the coefficients of organ masses were determined. Histological microscopic studies were performed on a LUMAN I2 microscope using an eyepiece 7 and a lens 40. To carry out statistical processing of the results, the Microsoft Excel and Statistica 6.0 application software package was used. Results. Preclinical studies were conducted in experiments on sexually mature autobred rats, males and females, to assess the toxicological properties of a new benzimidazole derivative, the compound RU-891, with 6-month intragastric administration at doses of 23 mg/kg (experimentally proven therapeutic dose) and 460 mg/kg (exceeding TD by 20 times). It was found that under the action of the substance RU-891 at a dose of 23 mg/kg, the general condition of the animals, body weight gain, hematological, biochemical, electrocardiographic parameters, as well as the functional state of the detoxification and excretion organs corresponded to the values of the control group. In studies on animals treated with the substance RU-891 at a dose of 460 mg/kg (20 TD), a gradual deterioration in the general condition was noted (an increase in body weight, most pronounced in male rats), activation of behavioral activity in females, but its suppression in males, changes dependent on the sex of animals in peripheral blood (increased erythrocyte levels and blood clotting time in male rats and no effect on these parameters in females), decreased excretory liver function, but activation of excretory kidney function, pathomorphological negative changes in the liver. In studies conducted one month after discontinuation of the administration of the compound RU-891 at a dose of 460 mg/kg, integral indicators (body weight gain, general condition, behavioral activity) in animals, as well as changes recorded from hematological, functional and structural pathomorphological disorders in the liver were practically leveled to control values, which probably may indicate the absence of pathological toxic effects of the studied substance RU-891 when administered orally to rats at a dose of 460 for 6 months. At the same time, taking into account the results of morphological and functional studies, it can be assumed that the RU-891 compound at a dose of 460 mg/kg has an effect on the liver as a “target organ”. However, this damaging effect of the studied compound on the detoxification function of the liver was reversible, since it was practically leveled to a state of control within a month after the cancellation of its administration to animals. Limitation. Sexually mature nonlinear rats of both sexes were used in the study, the number of individuals in the control and experimental groups was sufficient to obtain statistically significant results. Conclusion. PS RU-891 at a dose of 23 mg/kg with 6-month administration to rats is non-toxic and safe, since it does not cause irreversible changes in general condition, behavior, hematological parameters, biochemical parameters of blood and urine, and functional activity of the heart. With daily administration of PS RU-891 at a dose of 460 mg/kg, pathological effects on the liver and kidneys were revealed, which persisted during the withdrawal period.

Монография посвящена обоснованию способов нормализации воздушной среды подводных лодок после пожара и пожаротушения в концепции комплексной технологии управления пожарной безопасностью герметичных обитаемых отсеков. Особое внимание уделено обоснованию условий, обеспечивающих быструю нормализацию параметров воздушной среды после пожаротушения в части газового состава, давления и температуры.