


No 1 (2025)
Preventive toxicology
Assessment of the safety of short-term exposure of peat thermal degradation products in sublethal concentrations on rats
Abstract
Introduction. The lack of information about the health safety of firefighters and those taking part in extinguishing landscape fires from short-term exposure to sublethal concentrations of carbon monoxide determines the relevance of this work.
Material and methods. The study on rats used methods for assessing the state of the central nervous system, including behavioral tests, electroencephalography, morphology of the cerebral cortex, cardiac tissue, testes and liver. Chemical research methods included the determination of the content of CO and PM2.5 in the air of the exposure chamber. Genotoxicity on blood cells was determined by the DNA comet method.
Results. The experiment showed that exposure to peat smoke with a level of CO=99±2.5 mg/m3 and PM2.5=0.72±0.3 mg/m3 for 30 minutes had no pronounced adverse effect on male rats. The results of studying the motor research behavior of animals, EEG parameters, the structure of cardiomyocytes, epicardium, myocardium and pericardium did not differ from those in control rats. In the tissue of the sensorimotor cortex of the rats of the experimental group, an increase in the number of acts of neuronophagy was revealed, and in the liver tissue – a decrease in the number of polynuclear hepatocytes. In animals exposed to peat smoke, a decrease in the spermatogenesis index was revealed, which demonstrates a violation of the formation of germ cells of the final stages of spermatogenesis. No genotoxic effect was detected. Collectively, the identified changes may indicate a compensatory reaction of the rat body when ingested with toxicants.
Conclusion. The toxicity of a multicomponent mixture of forest biomass combustion products with short-term exposure, containing a CO concentration of 100 mg/m3, may be underestimated when predicting long-term effects on the reproductive potential of the adult population.
Limitation. It is caused by a number of uncertainties related to insufficient information about the short-term effects of high concentrations of CO and solid particles PM2.5 in the smoke of landscape fires on the nervous, reproductive, genome/epigenome system of male rats.
Compliance with ethical standards. The study was carried out in accordance with the rules of bioethics approved by the European Convention for the Protection of Vertebrates Used for Experimental and Other Purposes and approved by the Local Independent Ethical Committee of the Federal State Budgetary Scientific Institution “East Siberian Institute of Medical and Ecological Research” (Protocol No. 32 of 10.01.2023).
Author contribution:
Sosedova L.M. – concept, literature search, writing, article design, responsibility for the integrity of all parts of the article;
Vokina V.A. – concept, literature search, conducting an experiment, writing, statistical processing, editing an article;
Titov E.A., Novikov M.A., Tyutrina V.A. – collection and processing of material, statistical analysis.
All co-authors – approval of the final version of the article.
Conflict of interest. The authors declare no conflict of interest.
Acknowledgment. Thework was carried out according to the research plan within the framework of the state assignment.
Received: July 19, 2024 / Revised: November 2, 2024/ Accepted: December 18, 2024 / Published: February 25, 2025



Comparative assessment of toxic damage to the rats’ liver after subchronic exposure to nanoparticles of different chemical nature
Abstract
Introduction. Nanoscale particles, which are formed as a by-product of technological processes in the mining and metallurgical industries, pose high risks to workers’ health. The liver, as the center of detoxification processes in the body, is a target organ when almost any harmful chemical factors of the production environment enter the body, and their impact can cause the development of pathological processes in the liver.
The purpose of the study was to investigate the features of the hepatotoxic effect of various elementoxide nanoparticles (EO NPs) on an experimental in vivo model under subchronic exposure.
Material and methods. We examined hepatotoxicity of EO NPs in rats in three experiments with repeated intraperitoneal injections of NPs (1) PbO and CdO, (2) NiO, (3) CuO and SeO in total doses from 4.5 to 72 mg/kg body weight. Each experiment had its own control group. NPs were synthesized by laser ablation from pure metal plates. The assessment of hepatotoxicity in rats was carried out after the end of the experimental period according to the following indicators: liver mass, biochemical parameters of blood, cytological composition of liver cells and morphometric parameters in it.
Results. Of the NPs studied, NiO NPs and CdO NPs had the most pronounced hepatotoxic effect. At the same time, essential elements (such as selenium and copper) in the form of oxide nanoparticles at the studied doses had a hepatotoxic effect.
Discussion. Negative changes were observed following repeated intraperitoneal injections of different element oxide nanoparticles in all experimental animals, the most pronounced being related to exposures to CdO and NiO NPs. Alterations of biochemical parameters did not always correlate with structural damages revealed by histology and imprint cytology.
Limitations. The study is limited to examining toxic liver injury in only one animal species and sex.
Conclusion. The severity of the hepatotoxic effect of the studied nanoparticles (PbO, CdO, NiO, CuO, SeO) in a subchronic toxicological experiment on animals depends on their chemical nature.
Compliance with ethical standards. The experimental studies were approved by the local institutional ethics committee (protocols No. 2 of 01.02.2018, No. 4 of 01.02.2018, No. 2 of 20.04.2021).
Authors’ contribution:
Minigalieva I.A., Sutunkova M.P. – study concept and design, scientific editing of the text;
Klinova S.V., Kungurtseva A.K. – data collection and processing, preparation of figures, writing the text;
Valamina I.E. – histomorphological assessment;
Sahautdinova R.R. – data collection and processing, preparation of figures.
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: June 19, 2024 / Revised: September 27, 2024 / Accepted: December 18, 2024 / Published: February 25, 2025



Clinical toxicology
Intestinal lavage as a method of relief of alcoholic delirium in acute poisoning
Abstract
Introduction. Acute poisoning (AP) often occurs in people who abuse alcohol. The course of acute poisoning in such patients may be accompanied by alcohol withdrawal syndrome (AAS), a severe variant of which is delirium alcohol (AlD). Its formation aggravates the condition of patients, increases the risk of complications, increases the length of hospital stay and mortality. Standard methods of combating AlD may not be consistent with some aspects of the AP treatment paradigm, so the search for approaches to resolving this contradiction is relevant. One of the options for this approach may be the use of intestinal lavage (IL) as a method of relieving AlD in AP.
The aim of the study is to increase the effectiveness of therapeutic measures using intestinal lavage for delirium alcoholic against the background of acute poisoning with psychopharmacological drugs and corrosive substances.
Material and methods. We examined 106 patients, 59 of whom suffered from acute poisoning with psychopharmacological drugs (APPD) and 47 from acute poisoning with corrosive substances (APCS), who were in the department of acute poisoning and somatopsychiatric disorders of the N.V.Sklifosovsky Scientific Research Institute of Emergency Medicine of the Moscow City Health Department in 2019–2023, AlD developed.
The patients were divided into two groups: a study group of 56 patients, whose treatment complex included IL using enteral solution (ES) for the purpose of detoxification of endotoxemia and correction of homeostasis disorders, and a comparison group consisting of 50 patients who received standard therapy aimed at relieving AlD. The decision to use IL in the study group was made immediately after the diagnosis of AlD was established. IL using ES, which was administered through a nasogastric dual-channel tube, was carried out according to the method we developed. In 50 patients in the comparison group, standard AlD therapy was used. The compared groups of patients were comparable in severity of the condition, assessed in points on the DELIRIUM RATING SCALE-R-98, age and gender. The endpoints of the study were: duration of AlD, incidence of pneumonia, length of stay of patients in the intensive care unit and mortality.
Results. The severity of AlD, expressed in points on the DRS-R-98 scale, before the start of its relief in the study and comparison groups was comparable and, depending on the type of poisoning against which AlD developed, averaged from 28 to 31 points. The patients tolerated the inclusion of IL in the complex treatment of AlD against the background of acute respiratory distress syndrome and acute atrial fibrillation satisfactorily, without complications. AlD due to APCS was stopped after IL within 1 day, which is 8 times earlier than in the comparison group. This difference was statistically significant (p<0.05; criterion M–W). In case of APPD, the duration of AlD after IL was on average one day, and with standard treatment – 9 days. This difference in the timing of relief of AlD was statistically significant (p <0.05; criterion Mann–Whitney). It was found that against the background of AlD in patients with APCS, pneumonia developed in 23% of cases in the study group, and in 95.2% in the comparison group. Against the background of AlD in patients with APPD, these figures were 6.6 and 55.2%, respectively. The length of stay of patients with AlD in the intensive care unit during acute respiratory viral infection and acute atrial fibrillation in the study groups was on average 4 days, and in the comparison groups 6 and 7 days, respectively. Mortality in the same groups was 7.7 and 33.3% (APCS), and 10 and 17.3% (APPD), respectively.
Limitations. The research concerned the effectiveness of IL as a method of AlD relief in male and female patients, the limitations of which were: alcoholic delirium against the background of poisoning with psychopharmacological drugs and poisoning with corrosive substances, the age of patients (from 18–65 years), the volume of enteral solution 12 (9;15) liters for perfusion of the gastrointestinal tract during IL.
Conclusion. The inclusion of IL in the complex of treatment for AlD in AP contributes to a noticeable improvement in treatment results: reducing its duration against the background of APCS and APPD by 8 and 9 times, respectively; reducing the incidence of pneumonia by 4.1 and 8.4 times, reducing the length of hospitalization by 1.5 and 1.75 times, respectively. Mortality in the same groups was 4.3 and 1.73 times lower, respectively. Intergroup differences in all compared indicators were statistically significant (p<0.05; criterion χ2 and criterion Mann–Whitney).
Compliance with ethical standards. The protocol of this study was approved by the local ethics committee of the State Budgetary Healthcare Institution "Research Institute for Emergency Medicine named after N.V. Sklifosovsky" DZM No. 4-22 dated 04/26/2022. All participants gave informed voluntary written consent to participate in the study.
Authors contribution:
Vorobyova A.G. – collection of clinical material, statistical processing and analysis;
Matkevich V.A. – the idea, concept and design of the study, writing the text;
Potskhveriya M.M. – research design and organization;
Zubareva O.V. – research design, results;
Klyuev A.E. – organization and performance of laboratory tests, analysis of the data obtained.
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: May 29, 2024 / Revised: Jule 24, 2024 / Accepted: December 18, 2024 / Published: February 25, 2025



Acute cathinone poisoning: epidemiology, pathogenesis, clinical picture, diagnosis and treatment principles (literature review)
Abstract
Introduction. Acute poisoning with modern psychoactive substances and narcotic drugs is today among the main reasons for emergency hospitalization of people with acute poisoning.
Material and methods. The work summarizes information about epidemiology, pathogenesis, clinical picture, as well as diagnosis and principles of treatment of patients with acute cathinone poisoning.
Results. Cathinones are synthetic drugs that are similar in a number of ways, including their structure and mechanism of action to amphetamines and are used as psychoactive substances. The circulation of synthetic cathinones is under the control of the international community. Synthetic cathinones continue to hold the lead both in the number of new modifications created and in the volume of illegal trafficking, which drug control authorities are trying to suppress both in Russia and in neighboring countries. The class of synthetic cathinones today is quite numerous, although among users of surfactants their popularity varies, with the presence of clearly defined “market leaders”. These compounds may be substrates for presynaptic monoamine transporters (dopamine transporter, norepinephrine transporter, and serotonin transporter). Transporters responsible for reuptake of released monoamines from the synaptic cleft into the presynaptic neuron may be able to terminate the action of that monoamine at the postsynaptic receptor and facilitate recycling of the monoamine for re-release. In acute poisoning with cathinones, the clinical picture is nonspecific. It may manifest itself in the form of psychomotor agitation and/or hallucinations. In more severe cases, there are violations of life support systems. To determine α-PVP in biological objects (blood, urine, hair, nail sections), gas and liquid chromatography-mass spectrometry is usually used. Treatment of cathinone poisoning includes maintaining vital body functions: restoring hemodynamics, correcting electrolyte balance and relieving mental symptoms.
Limitations. The study was conducted by studying the databases Scopus, Web of Science, PubMed, Russian Science Citation Index, eLIBRARY, Cyberleninka.
Conclusion. A literature review of acute cathinone poisoning allows us to become familiar with the current problem of abuse of synthetic stimulants of the central nervous system. Studying the mechanisms of action, clinical manifestations, treatment and prevention allows us to form more informed approaches to this problem and develop effective measures to prevent and solve it.
Authors contribution:
Makarovskaya N.P. – the concept and design of research, writing the text;
Batotsyrenov B.V., Balabanova O.L., Evdokimova E.A. – collection and processing of materials;
Lodyagin A.N. – responsibility for the integrity of all parts of the article, writing the text.
All co-authors – approval of the final version of the article.
Conflict of interests. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Received: August 08, 2024 / Revised: August 28, 2024 / Accepted: December 18, 2024 / Published: February 25, 2025



Hyperendotoxinemia in severe oral poisoning with corrosive substances and intestinal lavage as a way to reduce its level
Abstract
Introduction. Elimination of hyperendotoxinemia in acute poisoning has life-saving significance, therefore it is an urgent task.
The aim is to assess the level of endotoxinemia in severe oral poisoning with corrosive substances and the effectiveness of intestinal lavage as a way to reduce its level.
Material and methods. Forty-seven women and men aged 47 (34.0; 57.5) and 42 (32.5; 54.5) years with severe oral poisoning with corrosive substances, acid or alkali, were examined. For the purpose of detoxification, 26 patients (study group) underwent five-hour intestinal lavage (IL) through a gastric tube in a volume of 12 (9; 13) liters. In the comparison group (21 patients), standard therapy was carried out. The endotoxin (ET) content in blood plasma in the study group was determined (before and after IL, and in the comparison group – before treatment and after 5 hours) on an Agilent 7890B gas chromatograph with an Agilent 7000 mass-selective detector. The reference values of ET concentration were 1.05–7.89 ng/ml.
Results. Before treatment, the ET concentration was 17.2 (9.68; 22.0) and 16.6 (15.3; 21.3) ng/ml, respectively, in the study and comparison groups, which exceeded the reference value by more than 2 times. After IL, its concentration decreased to 6.65 (13.0; 19.4) ng/ml – the level of reference values.
Against the background of standard treatment, the ET concentration decreased to 10.3 (7.56; 20.8) ng/ml, without reaching the reference value. Thus, after IL, the decrease in the ET level in the blood of patients was 1.6 times more pronounced than in the comparison group, the difference was statistically significant (p<0.05).
Discussion. The effectiveness of IL as a method of reducing the level of endotoxinemia in acute poisoning can be explained by the fact that as a result of intestinal cleansing, a depot of not only free lipopolysaccharide (as a chemical substance) is removed from it, but also as part of the oral gram–negative flora, an endotoxin producer, as a result of which the rate of entry of these pathogens into the blood stops or decreases. Against the background of the elimination of intestinal depot, the elimination of endotoxin from the blood is accelerated.
Limitations. The age of men and women is 18–65 years, oral poisoning with alkali or acid, the concentration of ET in the blood is above the reference value, the stages of the study are before treatment and after 5 hours, intestinal lavage in the volume of 9 to 13 liters.
Conclusion. In severe oral poisoning with corrosive substances, hyperendotoxinemia is detected. After 5 hours of IL, the concentration of ET in the blood of patients decreased by an average of 61.3%, reaching the reference value. Against the background of standard treatment, the level of ET in the blood decreased by an average of 38% without leaving the hyperendotoxinemia zone. The intergroup difference in the results was statistically significant (p<0.05; cr. U).
Compliance with ethical standards. The protocols of this study were approved by the local ethics committee of the N.V. Sklifosovsky Scientific Research Institute of Emergency Medicine of the Moscow City Health Department (protocols No. 5-16 of 11/21/2016 and No. 4-22 of 04/26/2022). All participants gave informed voluntary written consent to participate in the study.
Authors contribution:
Matkevich V.A. – the idea, concept and design of the study, writing the text;
Potshveriya M.M. – research design and organization;
Stolbova N.E. – data collection, systematization, statistical analysis;
Vorobyeva A.G. – ccollection of clinical material, statistical analysis;
Tyurin I.A. – organization and execution of chemical and toxicological research, analysis of the data obtained;
Maksimov A.A. – development of the methodology and implementation of the chemical-toxicological study, analysis of the obtained data.
All co-authors – approval of the final version of the article, responsibility for the integrity of all parts of the article.
Funding. The study had no sponsorship.
Conflict of interest. The authors declare no conflict of interest.
Received: August 8, 2024 / Accepted: December 18, 2024 / Published: February 25, 2025



Research methods
The experience of studying and possible ways to eliminate false-positive identification results when analyzing food products for the content of prohibited substances by high-performance liquid chromatography with tandem mass spectrometry method
Abstract
Introduction. The presence of prohibited compounds undeclared by the manufacturer in specialized food products (dietary supplements and sports nutrition products) is a violation of TR CU 021. However, the variety of chemical classes of prohibited compounds, their high biological activity and low effective concentrations determine the need for the use of highly sensitive chromatomass spectrometric methods for their detection. The aim of the work was to improve methodological approaches to identification during HPLC-MS/MS analysis of food products for the content of prohibited substances.
Material and methods. The study were carried out by HPLC with tandem mass-selective detection with ionization in electrospray in the target screening mode. Samples of dietary supplements and sports nutrition products were used as objects.
Results. The probable sources of false positive results of the analysis are considered and classified, examples from real practice are given. It is indicated that the main reasons for the appearance of false positive results may be: close values of the m/z precursor ions of the compounds being determined (the difference is less than 1 unit m/z); similarity of the structure of the compounds under study; the compound under study does not form a molecular precursor ion; matrix effects; cross-contamination.
Limitations. 5 main sources of identification errors associated with incorrect interpretation of mass spectra are analyzed.
Conclusion. The solution of the problems of reliable identification of prohibited compounds in dietary supplements is possible through the continuous development and improvement of screening methodology, the development of new methodological approaches, evaluation of their advantages and possible limitations.
Compliance with ethical standards. The study does not require the submission of the conclusion of the biomedical ethics committee or other documents.
Contribution of the authors:
Orlova O.I. – concept and design of research, writing text, editing;
Koryagina N.L. – processing of materials, writing text, editing.
All co-authors – approval of the final version of the article, responsibility for the integrity of all elements of the article.
Conflict of interest. The authors declare no conflict of interest.
Funding. The study had no sponsorship.
Accepted: December 25, 2023 / Revised: 06 May, 2024 / Received: / Published: February 25, 2025


