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Alexander S Pozdnyakov,1 Artem I Emel’yanov,1 Nadezhda P Kuznetsova,1 Tamara G Ermakova,1 Tat’yana V Fadeeva,2 Larisa M Sosedova,3 Galina F Prozorova11AE Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, 2Federal State Budgetary Scientific Institution Irkutsk Scientific Center of Surgery and Traumatology, Laboratory of Functional Genomics and Interspecific Interactions of Microorganisms, Irkutsk, 3East-Siberian Institute of Medical & Ecological Science, Department of Biomodeling & Translational Investigation, Angarsk, RussiaAbstract: New nontoxic hydrophilic nanocomposites containing metallic silver nanoparticles (AgNPs) in a polymer matrix were synthesized by the chemical reduction of silver ions in an aqueous medium. A new nontoxic water soluble copolymer of 1-vinyl-1,2,4-triazole and N-vinylpyrrolidone synthesized by free radical-initiated polymerization was used as a stabilizing agent. Transmission electron microscopy, scanning electron microscopy, ultraviolet–visible spectroscopy, Fourier transform infrared spectroscopy, X-ray diffraction, atomic absorption, and thermogravimetric analysis were used to characterize polymeric AgNPs nanocomposites. The results showed that the diameter of the synthesized AgNPs ranged from 2 to 6 nm. The toxicity of the initial copolymer of 1-vinyl-1,2,4-triazole and N-vinylpyrrolidone and its nanocomposite with AgNPs was found to be more than 5,000 mg/kg. The synthesized AgNP polymeric nanocomposite showed significant antimicrobial activity against different strains of Gram-negative and -positive bacteria. The minimum inhibitory concentrations suppressing the growth of the microorganisms ranged from 0.5 to 8 µg/mL and the minimum bactericidal concentrations ranged from 0.5 to 16 µg/mL. The fabricated AgNP nanocomposites are promising materials for the design of novel nontoxic hydrophilic antiseptics and antimicrobial components for medical purposes.Keywords: nontoxic nanocomposites, antimicrobial activity, silver nanoparticles, 1-vinyl-1,2,4-triazole, N-vinylpyrrolidone

Galina F Prozorova,1 Alexsandr S Pozdnyakov,1 Nadezhda P Kuznetsova,1 Svetlana A Korzhova,1 Artem I Emel'yanov,1 Tamara G Ermakova,1 Tat'yana V Fadeeva,2 Larisa M Sosedova31AE Favorsky Irkutsk Institute of Chemistry, Siberian Branch, Russian Academy of Sciences, Irkutsk, 2Scientific Center of Reconstructive and Restorative Surgery Siberian Branch of Russian Academy of Medicinal Sciences, Irkutsk, 3Institute of Occupational Health and Human Ecology, Siberian Branch of Russian Academy of Medicinal Sciences, Angarsk, RussiaAbstract: New water-soluble nontoxic nanocomposites of nanosized silver particles in a polymer matrix were synthesized by a green chemistry method. Nontoxic poly(1-vinyl-1,2,4-triazole) was used as a stabilizing precursor agent in aqueous medium. Glucose and dimethyl sulfoxide were used as the silver ion-reducing agents to yield silver nanoparticles 2–26 nm and 2–8 nm in size, respectively. The nanocomposites were characterized by transmission electron microscopy, ultraviolet-visible and Fourier transform infrared spectroscopy, X-ray diffraction, atomic absorption, and thermogravimetric data analysis. The nanocomposites showed strong antimicrobial activity against Gram-negative and Gram-positive bacteria.Keywords: silver nanoparticles, poly(1-vinyl-1,2,4-triazole), glucose, dimethyl sulfoxide, green synthesis

We studied the cytotoxic effect of gadolinium nanocomposite on cultured mouse fibroblasts 3T3-SV40 and histological changes in the liver tissue of albino rats after its administration. For in vitro experiment, gadolinium nanocomposite on the natural matrix of arabinogalactan (nGd-AG) was dissolved in DMEM nutrient medium to concentrations of 0.005, 0.02, 0.5, 2, and 5 mM. In in vivo experiment, a nGd-AG solution was orally administered to rats through a tube in a dose of 500 μg Gd/kg in 1 ml of 0.9% NaCl for 10 days. The pattern and degree of influence of the gadolinium nanocomposite on the studied cell culture depended on the concentration and duration of exposure. IC 50 of nGd-AG determined after cell incubation for 24, 48, and 72 h were 616 μg/kg (3.9 mM), 302 μg/kg (1.9 mM), and 222 μg/kg (1.4 mM), respectively. Histological changes in the liver of white rats induced by exposure to nanocomposite attested to the development of a compensatory reaction of the organ., (© 2023. Springer Science+Business Media, LLC, part of Springer Nature.)

This study aimed to follow the neurotoxic effect of peat smoke on adult outbred rats and its influence on central nervous system (CNS) parameters in first-generation offspring. Under experimental conditions, exposure to peat smoke was carried out on adult male Wistar rats for 24 h. After the end of the exposure, an open field test (OFT), electroencephalography (EEG), and histological analysis of the testes and brains of smoke-exposed males were performed, after which they were mated with intact females to obtain F1 offspring. Stillbirth, neonatal mortality, and body weight at 4, 7, 14, and 21 postnatal days, as well as behavior in the OFT and EEG parameters during puberty (3 months), were assessed. The results of the examination of F0 males showed a significant increase in motor activity and anxiety in the open field test and a violation of EEG parameters. Histopathologically, peat smoke caused a sharp increase in shadow cells (homogeneous cells with pale-stained cytoplasm, in which the cell and nuclear membranes are not visualized) and degeneratively altered neurons in the brain; we found no changes in the testicles. Peat smoke exposure during preconception did not affect neonatal mortality and weight gain in F1 offspring. Adult females born to peat-smoke-exposed males showed an increase in locomotor activity, and the behavior of adult F1 males did not differ from the control. In F1 males, a statistically significant increase in slow-wave activity indices in the delta band was observed.

The acute and subacute toxicity of a newly synthesized silver selenide nanoparticles encapsulated in a natural polymeric matrix of arabinogalactan study has been studied. The nanocomposite is a promising material for the design of diagnostic and therapeutic drugs. It can also be used for the preparation of fluorescent labels and in thermal oncotherapy. The employment of binary nanocomposites enables one to unveil the potential hidden in metals which constitute these composites. The study of acute toxicity, carried out by the oral administration of nanocomposites at a dose of 2000 mg/kg, has shown that the compound belongs to low-toxic substances of the 5th hazard class. With the subacute oral administration of nanocomposites at a dose of 500 μg/kg, slight changes are observed in the brain tissue and liver of experimental animals, indicating the development of compensatory-adaptive reactions. In the kidneys, the area of the Shumlyansky-Bowman chamber decreases by 40.5% relative to the control group. It is shown that the application of the protective properties of selenium, which is contained in the composite, helps to reduce the toxicity of silver.

We studied the reproductive function of albino male rats after long-term exposure to wildfire smoke and the species-specific behavior of their sexually mature offspring. After the end of exposure, the mean number of spermatogonia and the relative number of Leydig cells in rat testes decreased and the index of spermatogenesis decreased. The offspring of exposed males mated with intact females demonstrated impaired cognitive abilities and disturbances of species-specific behavior. The severity of these changes depended on time interval between the end of the inhalation exposure and mating., (© 2022. Springer Science+Business Media, LLC, part of Springer Nature.)

The aim of our investigation was to make a comparative assessment of the biological effects of silver nanoparticles encapsulated in a natural and synthetic polymer matrix. We carried out a comparative assessment of the biological effect of silver nanocomposites on natural (arabinogalactan) and synthetic (poly-1-vinyl-1,2,4-triazole) matrices. We used 144 three-month-old white outbred male rats, which were divided into six groups. Substances were administered orally for 9 days at a dose 500 μg/kg. Twelve rats from each group were withdrawn from the experiment immediately after nine days of exposure (early period), and the remaining 12 rats were withdrawn from the experiment 6 months after the end of the nine-day exposure (long-term period). We investigated the parietal-temporal area of the cerebral cortex using histological (morphological assessments of nervous tissue), electron microscopic (calculation of mitochondrial areas and assessment of the quality of the cell nucleus), and immunohistochemical methods (study of the expression of proteins regulating apoptosis bcl-2 and caspase 3). We found that the effect of the nanocomposite on the arabinogalactan matrix causes a disturbance in the nervous tissue structure, an increase in the area of mitochondria, a disturbance of the structure of nerve cells, and activation of the process of apoptosis.

The use of a developed experimental model of a natural fire made it possible to assess the consequences of 24 h exposure to peat combustion products in albino rats. Peat smoke exposure leads to behavioral disturbances in rats, characterized by an increase in locomotor activity and an increased level of anxiety. Indicators of brain bioelectrical activity of the exposed animals supported the state of anxiety and psychoemotional stress. Epigenetic changes in the blood cells of exposed animals were revealed under 24 h exposure to peat smoke, characterized by a decrease in the level of global DNA methylation.

Particular concern at the present stage is the health effects of wildfires' smoke. The aim of the study was to determine the impact of paternal biomass-smoke exposure on offspring's behavior and cognitive abilities. Male rats were exposed to biomass smoke for four hours/day, five days/week, for four weeks. Average concentration of carbon monoxide and particulate matter of 2.5 μm PM 2.5 in the chamber during exposure were 28.7 ± 5.3 mg/m 3 and 1.9 ± 0.5 mg/m 3 , respectively. At the same time, high concentrations of furfural and acetaldehyde were detected in the air environment of the exposure chambers. Offspring was obtained by mating of experimental males with untreated females, immediately after the end of the exposure and after 60 days (long-term period). Offspring were tested by using the Morris water maze and open field at three months of age. Male and female offspring born by mating immediately after exposure demonstrated decreased exploratory behavior, locomotor activity, and spatial navigation, as well as increased anxiety levels. Locomotor and exploratory activity in rats of both sexes from progeny obtained after long-term exposure to smoke had no statistically significant differences when compared to the control; however, the females showed a high level of anxiety and impaired cognitive functions. The recovery period after biomass-smoke intoxication, comparable in duration of spermatogenesis in rats, was an important factor in reducing the risk of developing central nervous system (CNS) disorders in offspring., Competing Interests: The authors declare no conflict of interest.

Experimental studies of Perchlozone, an antituberculous drug with manifest inhibitory activity towards Mycobacterium tuberculosis and Mycobacterium bovis, were carried out. Genotoxicity of Perchlozone was evaluated by the DNA comet method on liver and lung tissues and blood cells after 14-day inhalation exposure of rats. The level of DNA aberrations in response to inhalations of the drug in a concentration of 102.6±13.7 mg/m 3 increased in lung tissue but not in the blood cells or liver. These results indicated genotoxic activity of antituberculous drug Perchlozone.

The contribution of prenatal hypoxic damage to the CNS to the formation of high sensitivity of the body to lead acetate was studied. Prenatal fetal hypoxia was modeled by the administration of sodium nitrite in doses of 5, 25, and 50 mg/kg to pregnant female rats. Cognitive capacities of mature offspring were evaluated in the radial maze test and Morris water maze test. After attaining learning criterion in the radial maze, lead acetate in a dose of 80 mg/kg was added to the drinking water of all animals over 2 weeks. Testing was performed during the exposure to the agent until disruption of the conditioned behavior. It was found that severe prenatal hypoxia (induced by the administration of 50 mg/kg sodium nitrite) impaired spatial memory, increased latency of funding the platform in Morris water maze test, and serves as a factor contributing to earlier manifestations of the neurotoxic effects of lead acetate.

In lead intoxication model, with hyperglycenia state, atherogenicity coefficient reached 1,45 (1,35-1,85), if compared to 1,30 (0,85-1,40) in white rats exposed to lead. Heart rate reached 421,00 (411,00-468,00) per minute vs, 385,50 (359,00-399,50) per minute in animals died with lead intoxication, shorter median interval between QRS-complexes up to 143,00 (128,00-146,00) ms vs, 160,00 (150,50-169,00) ms was seen in animals exposed to lead.

The article presents results on experimental modelling an influence of silver nanoparticles incorporated into natural polymer arabinogalactane matrix on brain tissue of white outbred rats. The rats underwent parenteral injection of silver nanoparticles incorporated into polymer arabinogalactane matrix (dosage of 100 and 500 micrograms of silver per kg of the animal weight). The studies covered expression of 2 proteins participating in apoptosis process, in mitochondrial activation type - caspase-3 and protein bcl-2. During experiment, the groups examined demonstrated significant dose-dependent effect of bcl- 2 protein expression and increased number of caspase-3 expressed and non-expressed hyperchromic cells under exposure to argentumarabinogalactane - that indicates disorders of cellular structure and apoptosis development.

There was executed the study of the impact of toluene on indices of behavior, cognitive capabilities and bioelectric activity of the brain in white rats with normal course of the period of antenatal development and against background ofprenatal hemic hypoxia Prenatal hypoxia was modeled in pregnant female rats by subcutaneous injection of sodium nitrite in a dose of 50 mg/kg at from the 10 to the 19 day of gestation. At the age of 3 months the males from the obtained offspring were exposed to inhalation exposure of toluene (150 ppm, 4 weeks). After exposure to toluene in animals there was evaluated the pattern of individual behavior, indices of cognitive capabilities and also bioelectric activity of the brain. There were revealed such common consistencies of transformations in the behavior of exposed to toluene animals with normal and impaired embryogenesis as disturbed motor activity, reduction of exploratory behavior and cognitive functions, impaired bioelectric potentials of the brain. Features of changes in behavior and EEG indices in toluene-exposed rats with prenatal hypoxia are characterized by inhibition of motor activity, increased anxiety and latency of main peaks of auditory and visual evoked potentials. Prenatal hypoxic damage of the central nervous system was shown to be an aggravating factor in toluene intoxication in rats.

There are presented results of the immunohistochemical study of neural tissue of outbred albino rats exposed for 9 days to the influence of the silver nanobiocomposite consisted of silver nanoparticles encapsulated into a matrix of a natural polymer - arabinogalactan. The research of albino rats was performed in 2 stages: half of the rats in each groups were decapitated immediately after the exposure (early period) and the rest animals - 6 months after the end of exposure (remote period). The impact of the studied substance was proved to cause functional changes in cells of the nervous tissue. After the subacute administration of the nanobiocomposite - argentum-arabinogalactan (nano-Ag-AG) in cells of the nervous tissue of the brain of albino rats the expression of apoptotic and anti-apoptotic protein (caspase-3 and bcl-2) was established to be changed. The number of normal neurons producing protein caspase-3 sharply increases. Herewith the number of immunonegative neurons fairly declines. Along with this there is noted the high level of bcl-2 content, one function ofwhich is the preclusion ofapoptosis. In preparations there is revealed a significant gain in the number of bcl-2 expressing neurons, however, the protective effect of the protein is not fully realized, that leads to the significantly increase in the content of damaged hyperchromatic cells. The evaluation of results of the immunohistochemical study of the nervous tissue of albino rats according to data concerning the proteins caspase-3 and bcl-2 expression permits to make a conclusion about the capability of nanoargentum encapsulated into polymer matrix by passing the blood-brain barrier to induce the triggering apoptosis cascade in neurons of the cerebral cortex.

The paper present experimental materials of intragastric administration of silver nanoparticles encapsulated in polymer matrix of arabinogalactan by white outbred male rats. Animals were injected "pure" arabinogalactan and colloid silver solution containing silver macroform separately for comparison. Research provided data about status of brain tissue at the impact of these substances on organism. Histological analysis revealed the presence of a pathological process, character and intensity of which varied depending on the type of injected material. Pathological process under the influence of silver-arabinogalactan characterized by appearance in brain tissue of perivascular edema and development of acute inflammation in formation of glial scars, swelling of vascular bundles in sum.

The article presents results of histologic and immunohistochemical examination of nerve tissue of outbred white rats subjected over 9 days to nanobiocomposite containing nanoparticles of silver and natural biopolymer arabinogalactane. Exposure to the studied chemical was proved to cause structural and functional changes in nervous tissue. Comparing results of structural study of nervous tissue with expression of proteins caspase-3 and bcl-2 proves ability of nanosilver incapsulated into polymer matrix to penetrate through blood-brain barrier and induce apoptosis in neurons of brain cortex.

In the materials there are presented features of methodological approaches in the performing of experimental studies concerning of the investigation of the impacts of environmental factors on the human body. There were shown the results of our experiments performed at the Institute, in the modeling of biological effects of antimicrobial nanobiocomposites with nanosilver particles, toxic encephalopathy, in the study of the combined effect of the factors of biological and chemical nature. There was proved the importance of intracellular of proteomics in the assessment of the effects of the action of nanoparticles and nanomaterials on the body. There were revealed key parts of progredient course of mercury poisoning in the long-term. The special section is presented by the study of long-term effects of anthropogenic environmental factors on subsequent generations. There are presented results witnessing to a deterioration of the functional state of the central nervous system in rats in the first and second generations, whose parents were exposed to neurotoxicants. There was proved the aggravating role of prenatal hypoxia in the development of toxicity in rats in sexually mature age. Experimental biomodeling is aimed at sighting of pathogenetically substantiated treatment and preventive measures: initially, in experimental conditions, and in the future in the rehabilitation of sick or injured patients.

The article covers results of long-standing study of clinical features of occupational neurointoxications in late period, and mechanisms underlying nervous system disorders in individuals working under long exposure to neurotoxic chemicals and in late period of occupational intoxications. With modern neurophysiologic, neuropsychologic, immunologic and biochemical diagnostic methods, the authors specified early manifestations of occupational disorders. Translation patterns of neurointoxications are specified.

Comparative study covered influence of toluene on behavioral parameters, cognitive abilities and brain bioelectric activity in white rats with normal embryonic development or with prenatal hypoxia. Prenatal hypoxia was simulated by subcutaneous injection of 50 mg/kg sodium nitrite into female white rats on day 13-14 of gestation. The offspring at the age of 2, 5-3 months was exposed to toluene (concentration of 560 mg/m3, 4 hours per day, 5 days per week, over 4 weeks). After the exposure, the animals were estimated for individual and intraspecific behaviour in "open fields and "resident-intruder" tests, for cognitive abilities in "radial maze" training, EEG with visual and auditory evoked potentials. Acute hypoxia at early stages of organogenesis appeared to be burdening factor and to influence consequences of toluene intoxication.

The features of the methodical approaches in performing the experimental studies dealing with studying the working condition and the health state in the employees are presented in this paper. The results of our experiments performed in the Institute based on modeling the occupational toxic encephalopathy, studying the combined factor activity of the biological and chemical nature developing the methodical approaches to the assessment of the biological activity effects of the nanomaterials are indicated. The purposefulness of performing the experiments in the occupational medicine using the non-breedy and line-breedy animals is considered.

The paper provides the results of experimental studies of the impact of vinyl chloride or sublimate intoxication in male albino rats on the functional state of the nervous system of their offspring. Retarded sensorimotor development was revealed in the neonatal offspring. The pubertal offspring showed behavioral pattern disintegrity that was characterized by changes in motor activity and orientative-exploratory responses and by anxiety. There was abnormal impulse conduction in the neuromuscular apparatus of the hind legs of albino rats and morphological changes in the structure of nervous tissue.

Experiments on laboratory animals studied toxic effects of benzofuran derivatives obtained during anti-arrythmic drug Amiodarone production. Toxic effects were studied for single and subacute intake through intragastric, inhalation and epicutaneous routes. Recommendations are given for hygienic regulation of Amiodarone and intermediate products of its synthesis in the air of workplace.

The paper provides the results of experimental risk assessment of exposure to a biological factor combined with a chemical factor, which present with the protein-bearing dust and sulfur dioxide. The regularities and specific features of the functioning of the body's physiological systems have been revealed in the development of responses to combined exposure to biological and chemical factors, which show that the response may take three basic paths: sensitization, allergopathy, and toxic allergopathy. The essentials of the methodology evaluating and predicting the nature of the biological effects of a response in the experimental study of combined exposure to biological and chemical factors of the nature have been developed.

The article covers results of experimental modelling under exposure to biologic factor associated with chemical factor, and neurotoxic process caused by injection of vinylchloride, inorganic mercury compounds and toxic chemical complex. The authors specified methodologic approaches to evaluate and forecast character of biologic effects in laboratory animals response to influence of environmental factors.

The article covers results of long-standing research on clinical peculiarities and course of toxic encephalopathy in distant period of occupational neurointoxications, on main concepts and pathogenetic steps of formation and progress of toxic encephalopathy. Through investigation covered firemen after exposure to complex of toxic chemicals and patients in post-contact period of chronic mercury intoxication. Modelling of chronic inhalation of metallic mercury vapors was performed.

The paper analyzes the results of microbiological, immunological, and cytological studies of the upper airway in apparently healthy individuals exposed to toxic agents. The upper airway endoenvironmental changes have been found at the prenosological level, which may lead to the development of clinical pathology. The informative indicators of prenosological diagnosis have been determined, which make it possible to detect early changes in microbiocenoses, the body's resistance, and mucosal cytological status.

Microbial contamination of the upper airway mucosa and skin was quantified and the salivary concentrations of lysozyme and secretory immunoglobulin A were determined in persons exposed to toxic substances. The antagonistic activity of the intestinal microflora was studied in firemen. Lower resistance was revealed in firemen and gas rescuers upon exposure to poor factors during their activity.

The article deals with influence of longstanding inhalation of mercurial vapors on behavior of white rats, on morphologic and functional disorders in nervous system, on peculiarities of neuromediators metabolism in brain homogenate over the post-contact period.

Results of quantitative and qualitative assessment of mucosal microbiocenoses in the upper respiratory tracts are presented along with cytomorphological characteristics of upper airway mucosa. SIgA and lysozyme concentrations were measured in the saliva of firemen. Their exposure to occupational hazards during periods of professional activity was shown to lead to a decrease in non-specific anti-infectious resistance to the effect of unfavourable factors.

Morphofunctional disturbances in rats affected vinyl chloride in remote period of intoxication. The presented data concern influence of inhalation impact of vinyl chloride on nervous system of white rats in remote period.

The article covers problem of experimental biologic modelling of toxic encephalopathies. The authors represent major methodic approaches to modelling, criteria and methods to evaluate pathologic condition of CNS, present results of own research in creating models of toxic encephalopathies caused by metallic mercury and vinylchloride inhalation.

Prolonged inhalation of metallic mercury vapors by white rats appeared to result in toxic encephalopathy manifesting in disorders of orientative and investigatory, emotional behavior - increased anxiety, aggressiveness, negative e motionalism, higher locomotion activity. Throughout the experiment the animals had increased aggressiveness and muscular tone.

Microbiocenoses were qualitatively and quantitatively determined; the cytomorphological parameters of the upper respiratory tract mucosae were studied, and the concentrations of SIgA were measured in the saliva of firemen. In the latter, nonspecific infection resistance was found to diminish due to the influence of poor occupational factors. A strong correlation was found between the influencing factors and the development of upper airway diseases; the latter were greatly affected by occupational factors.

Differences in the metabolic status of peripheral blood lymphocytes were observed after exposure of intact guinea pigs and animals sensitized with biological allergens to sulfur dioxide. When sensitization was complicated by chemical exposure, enzyme activities in lymphocytes depended on the type of allergen and degree of hypersensitivity.

Peripheral lymphocytes reaction--lower succinate dehydrogenase activity, nonspecific esterase activity and stimulated lactate dehydrogenase--after combined biologic and chemical influence suggests progressive allergic process, depends on severity of antigen load and is not detected for separate factors influence.

Immune and allergologic criteria specified describe human response to combined action of chemical and biologic factors. The authors suggested the most important and informative criteria differentiating the response variants.