No 5 (2021)

Reviews

Universality of the phenomenon of «neurotoxicity» (literature review)

Golovko A.I., Ivnitsky J.J., Ivanov M.B., Rejnyuk V.L.

Abstract

Introduction. The neurotoxic effect is considered as one of the variants of the toxicity of many xenobiotics. Neurotoxic effects develop not only in poisoning, but also when exposed to biological (for example, pathogens of infectious diseases) and physical (for example, ionizing and non-ionizing radiation) factors.

Materials and methods. The subject of the analysis was the phenomenon of neurotoxicity. The information was obtained by studying the databases Scopus, Web of Science, PubMed, RSCI.

Results. The absence of a single definition of the concept of «neurotoxicant» is noted. In addition to chemicals, other factors have neurotoxicity: biological, physical. The mechanisms of neurodegeneration under the influence of neurotoxicants with different mechanisms of action are similar and include excitotoxicity, neuroinflammation, suppression of mitochondrial function, inhibition of neurogenesis and gliogenesis, oxidative stress, increased BBB permeability and apoptosis. The presented features allow us to speak about the universality of the phenomenon of «neurotoxicity».

Conclusion. When considering the phenomenon of «neurotoxicity», certain difficulties arise. A clear idea of the etiological factors of this phenomenon is not fully formulated. A comprehensive classification of neurotoxicants has not been created. At the same time, the processes of neurodegeneration are very similar in cases of poisoning with neurotoxicants with different mechanisms of action, which proves the universality of the phenomenon of «neurotoxicity.

Toxicological Review. 2021;29(5):4-16
pages 4-16 views

Carbon monoxide: modern concepts to the treatment of acute poisonings (literature review)

Grebenyuk A.N., Bykov V.N.

Abstract

Introduction. Carbon monoxide (CO) is one of the most common causes of chemical injuries and the main toxic factor in the people death in fires. The mechanism of the toxic effect of CO, associated with the formation of carboxyhemoglobin and the development of hypoxia, determines the rapid development of the clinical picture of acute intoxication and the need for emergency first aid and medical care to the poisoned. 

Material and methods. Literature sources, summarized in the bibliographic databases eLIBRARY.RU, PubMed and Scopus, were the material for analysis.

Results. First aid is based on quickly removing the victim from the fire zone or other area with a high concentration of CO and providing him with oxygen as soon as possible. During medical evacuation, it is necessary to carry out continuous inhalation of 80–100% oxygen, to ensure rest and warmth of the victim. In the emergency department of the hospital, oxygen inhalation and maintenance therapy should be continued, clinical and laboratory diagnostic measures aimed at assessing the severity of intoxication, identifying complications and concomitant pathology should be performed. In the case of severe CO poisoning, medical care continues to be provided to the victims in the intensive care unit or in the oxygen-barotherapy unit. The main antidote for CO poisoning is oxygen, which can be used in two versions – normobaric or hyperbaric oxygenation. As a pharmacological antidote to CO, zinc bisvinylimidazole diacetate (acizol) which can accelerate the breakdown of carboxyhemoglobin, improve the oxygen-binding and gas-transport properties of blood, as well as the dissociation of oxyhemoglobin in tissues is used. Along with antidotes, an important role in the treatment of CO poisoning is played by pathogenetic and symptomatic therapy aimed at the prevention and treatment of toxic encephalopathy, brain edema, cognitive dysfunction, toxic myocardiodystrophy and arrhythmia, prevention of pneumonia, correction of the acid-base state, compensation of the energy needs of the body, etc.

Conclusion. Further improvement of existing means and methods for the treatment of intoxication, the development and introduction of new antidots into medical practice will increase the effectiveness of therapeutic measures, reduce the number of deaths and disabilities after acute poisoning with carbon monoxide.

Toxicological Review. 2021;29(5):17-24
pages 17-24 views

Original articles

Study of toxicity and peculiarities of biological effects of nanocomposite pectin-Ag: results of a subchronic experiment

Vasilkevich V.M., Bogdanov R.V., Gilevskaya K.S., Kulikouskaya V.I.

Abstract

Introduction. Nanocomposites synthesized by the “green chemistry” method do not contain toxic chemicals (reducing agents and organic solvents) as carriers and/or stabilizing shells. One of the representatives of this group of materials are nanocomposites based on silver, which are increasingly used in medical practice, veterinary medicine, and in some other fields.

Material and methods. The nanocomposite is Ag0 nanoparticles coated with a highly methoxylated pectin shell. The concentration of Ag0 nanoparticles in the hydrosol of the pectin-Ag nanocomposite is 1.65 mmol/l, and the pectin content is 7.5 mg/ml. The size of the synthesized pectin-Ag nanocomposite is ~20–30 nm, more than 90% of the particles have a diameter of less than 20 nm, the value of the ξ-potential is 45.3 ± 0.7 mV. Toxicological studies were carried out on outbred rats. The main goal of the research was to study the toxic effects of the pectin-Ag nanocomposite in a subchronic experiment (90 days). At the end of the experiment, a complex of behavioral and clinical and laboratory parameters was determined, which made it possible to assess the biological effect of the nanocomposite on animals. The research results were statistically processed.

Results. With subchronic intragastric administration of the pectin-Ag nanocomposite to laboratory animals (rats) for 3 months at doses of 50, 500, and 5000 mg/kg, it was found that the nanocomposite exhibits a dose-dependent general toxic effect with critical target organs - the liver and spleen and the main biochemical markers of toxicity effect - aminotransferase, alkaline phosphatase and lactate dehydrogenase.

Conclusion. Experimental studies have made it possible to substantiate the threshold doses of the hydrosol of the pectin-Ag nanocomposite for the intragastric route of intake.

Toxicological Review. 2021;29(5):25-33
pages 25-33 views

About the threshold concentration of nickel oxide nanoparticles in long-term inhalation exposure of rats

Katsnelson B.A., Chernyshov I.N., Solovyeva S.N., Minigalieva I.A., Gurvich V.B., Valamina I.E., Makeyev O.H., Sahautdinova R.R., Privalova L.I., Tsaregorodtseva A.E., Korotkov A.V., Shuman E.A., Panov V.G., Sutunkova M.P.

Abstract

Introduction. Nickel oxide nanoparticles are of interest for toxicological science, not only as engineered nanoparticles, producing for industrial and scientific needs, but also as spontaneous pollutants of the atmosphere and the working area in industrial processes related to metallurgy and welding.

Materials and methods. Rats were exposed to nickel-oxide aerosol at a concentration of 2.4 ± 0.4 µg/m3 in a “nose only” inhalation setup for 4 hours at a time, 5 times a week, during an overall period of 2 weeks to 6 months. 

Results. Of the several dozen examined parameters, only a few statistically significant manifestations associated with the reaction of the deep airways to inhaled nanoparticles were noted. However, in the biochemical and morphometric parameters of the lungs, even at the longest periods of exposure, the intergroup differences were insignificant. At the same time, even from the first weeks of the exposure period, genotoxic and allergic indices shifts are detected.

Conclusion. For most of the evaluated effects, this level of exposure to nickel oxide nanoparticles may be considered as close to LOAEL, or even to NOAEL. However, according to some indicators, there are effects that suggest a non-threshold nature.

Toxicological Review. 2021;29(5):34-42
pages 34-42 views

Development of enzyme immunoassay for detecting I and II types of shiga-like toxins

Kuklina G.V., Pechenkin D.V., Ipatov S.S., Eremkin A.V., Kytmanov A.A., Tikhvinskaya O.V.

Abstract

Introduction. The aim of the work was development of enzyme immunoassay for detecting I and II types of shiga-like toxins and assessment of it diagnostic properties. 

Materials and methods. For the research, we used hybridomas producing monoclonal antibodies to shiga-like toxins of types I and II, obtained at the branch of the Federal State Budgetary Institution “48 Central Research Institute” of the Ministry of Defense of Russian Federation (Kirov); BALB/c mice; shiga-like toxins of types I and II. Hybridoma cells were cultured in culture flasks and in the peritoneal cavity of BALB/c mice. Monoclonal antibodies were isolated from ascitic fluids by precipitation with a saturated solution of ammonium sulfate, followed by purification by ion exchange chromatography. The obtained preparations of monoclonal antibodies were used to develop enzyme immunoassay for the detection of shiga-like toxins of types I and II. Specific components of enzyme immunoassay were freeze-dried in a protective environment.

Results. As a result of research, preparative quantities of monoclonal antibodies against I and II types of shiga-like toxins were obtained and purified; selection of monoclonal antibodies for sorption on the solid phase and for the synthesis of immunoperoxidase conjugates was carried out. 

Conclusion. Experimental enzyme immunoassay allowing to identify 1 ng/ml I and II types of shiga-like toxins in «sandwich»-ELISA was developed.

Toxicological Review. 2021;29(5):43-48
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Analysis of the toxicological situation in Moscow in the first three months of the COVID-19 pandemic

Simonova A.Y., Rozhkov P.G., Belova M.V., Ilyashenko K.K., Potskhveriya M.M., Ostapenko Y.N., Goldfarb Y.S., Fetisova A.I., Elkov A.N., Sokolova T.A.

Abstract

Introduction. On March 11, 2020, WHO announced the global COVID-19 pandemic. According to literature data, the spread of coronavirus infection COVID-19 affected the structure of acute chemical poisoning.

The aim. Assessment of the impact of the COVID-19 pandemic and restrictive measures on the peculiarities of seeking advice and the structure of acute chemical poisoning in Moscow. 

Material and methods. The data of the registration forms “Card of recording of a consultation of a patient with acute poisoning of chemical etiology” in the period from March 30 to June 30, 2020 and 2019 were studied. The analysis indicators of a hospitalization of patients in the department of acute poisoning and somatopsychiatric disorders of N.V. Sklifosovsky, the Research Institute of Emergency Medicine.

Results. It was found that in the analyzed period of 2020 compared to 2019, the proportion of injured people of working age decreased by 11.2%, while it increased at the age of 0-17 years by 3.2 times. An increase in the number of consultations for individuals by 2.1 times was noted. There was an increase in the number of complaints about poisoning with antibiotics, drugs from the T45 group (anticoagulants, vitamins, etc.), T37 (antiviral, anti-microbial, etc.) by 1.7-2 times. 

In March-June 2020, there was an increase in the number of complaints about the toxic effects of alcohol (T51), an increase in hospitalized patients with acute alcohol poisoning by 4 times, and with combined alcohol poisoning – by 2.7 times. The number of complaints about poisoning with detergents and disinfectants in the first three months of the pandemic increased by 2.7 times.

Conclusion. The pandemic and the introduction of restrictive measures for COVID-19 have affected the toxicological situation in Moscow, which must be taken into account when determining the guidelines for organizational measures for the provision of medical care for acute chemical poisoning during the COVID-19 pandemic.

Toxicological Review. 2021;29(5):49-57
pages 49-57 views

New Information

Toxicological assessment of Capparis spinosa L. seed’s oil

Poghosyan S.B., Tadevosyan N.S., Muradyan S.A., Ter-Zakaryan S.H., Jzhandzhapanyan A.N., Kirakosyan G.V.

Abstract

Introduction. Herbal medicines are unique therapeutic agents that represent multicomponent complexes of biologically active substances. They have low toxicity, a wide spectrum of therapeutic action with a minimum of side effects and a relatively low cost. Capparis spinosa L. has been widely used in traditional medicine for the treatment of various diseases and health conditions.

Material and methods. An assessment of the toxicometric parameters of Capparis spinosa L. seed’s oil was done by a single oral and dermal exposure, the average lethal doses have been calculated for both routes, sensitivity by sex has been studied. The local irritant, skin resorptive, effect on the mucous membranes of the eyes of experimental animals was investigated. Sensitizing activity was studied according to the complex sensitization scheme. Processing of the results was carried out by the method of variation statistics. Standard errors and other indicators were calculated using the Litchfield-Wilcoxon probabilistic analysis method modified by Prozorovsky. The difference in mean values was estimated using Student’s t-test.

Results. The acute toxicity of the oil was not expressed, death of animals was not observed. Average lethal dose for a single oral exposure was above 7000 mg/kg and dermal more than 3000 mg/kg. Sensitivity by sex in an acute experiment has not been established. The oil had a mild irritating effect on the mucous membranes of the eyes. It did not show skin-irritating, resorptive-toxic and sensitizing effects. 

Conclusion. Capparis spinosa L. seed’s oil belongs to the 4th hazard class (low hazard) according to the hygienic classification and safety requirements of substances.

Toxicological Review. 2021;29(5):58-63
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Jubilees

BORIS ALEKSANDROVICH KATSNELSON (to the 95th birthday anniversary)

Article E.

Abstract

20 октября 2021 г. исполнилось 95 лет со дня рождения Заслуженного деятеля науки Российской Федерации, действительного члена Нью-Йоркской Академии наук, доктора медицинских наук, профессора Бориса Александровича Кацнельсона.

Toxicological Review. 2021;29(5):64-64
pages 64-64 views