Analysis of Experimental Data on Changes in Various Structures and Functions of the Rat Brain following Intranasal Administration of Fe2O3 Nanoparticles

Particulate matter, including iron nanoparticles, is one of the constituents of ambient air pollution. We assessed the effect of iron oxide (Fe2O3) nanoparticles on the structure and function of the brain of rats. Electron microscopy showed Fe2O3 nanoparticles in the tissues of olfactory bulbs but not in the basal ganglia of the brain after their subchronic intranasal administration. We observed an increase in the number of axons with damaged myelin sheaths and in the proportion of pathologically altered mitochondria in the brains of the exposed animals against the background of almost stable blood parameters. We conclude that the central nervous system can be a target for toxicity of low-dose exposure to Fe2O3 nanoparticles. © 2023 by the authors.Ministry of Education and Science of the Russian Federation, Minobrnauka; Ural Federal University, UrFUThe analysis was supported by the Ministry of Science and Higher Education of the Russian Federation within the “Priority—2030” Development Program of the Ural Federal University; the experimental data were provided by Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

The evaluation of the anti-genotoxic effectiveness of a complex of bioprotectors under chrysotile asbestos exposure

On the background of the influence of bio-protective complex, it is shown the weakening of mutagenic effect estimated has been demonstrated in a micronuclear assay on the bone marrow cell of linear mice after intraperitoneal injection of chrysotile asbestos. It was demonstrated also that administration of this complex in children influenced beneficially the lipoperoxidation and cytogenetic index in cells of buccal mucosa and DNA fragmentation in blood leucocytes. These effects may be considered as an evidence for a probable anticancerogenic action of the tested biological prophylaxis.На фоне влияния комплекса биопротекторов показано ослабление мутагенного действия в микроядерном тесте (МЯТ) на клетках костного мозга у линейных мышей при внутрибрюшинном введении хризотил-асбеста, а также после проведения контролируемого курса биопрофилактки на основе того же комплекса у детей, проживающих в г. Асбесте, по данным МЯТ на клетках буккального эпителия, а также по снижению коэффициэнта фрагментации ДНК лейкоцитов крови. Эти эффекты могут расцениваться как свидетельствующие о вероятном противоканцерогенном действии испытанной биологической профилактики

Electron microscopy study on the transport of lead oxide nanoparticles into brain structures following their subchronic intranasal administration in rats

White outbred female rats were exposed intranasally to 50-µL of suspension of lead oxide nanoparticles (PbO NPs) at a concentration of 0.5 mg/mL thrice a week during six weeks. A control group of rats was administered deionized water in similar volumes and conditions. The developed intoxication was manifested by altered biochemical and cytochemical parameters, as well as behavioral reactions of animals. Using electron microscopy and energy-dispersive X-ray spectroscopy techniques, we revealed deposition of PbO NPs in the olfactory bulb, but not in basal ganglia, and an increase in the number of axons with damage to the myelin sheath in the tissues of olfactory bulb and basal ganglia, changes in the ultrastructure of mitochondria of neurons in the tissues of olfactory bulb and basal ganglia of the brain, and differences in the mitochondrial profile of neurons in different regions of the rat brain. Our results collectively suggest that the central nervous system may be a target of low-level toxicity of lead oxide nanoparticles. © 2022, The Author(s).Ural Federal University Program of DevelopmentYekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial WorkersMinistry of Education and Science of the Russian Federation, MinobrnaukaThe research funding from Yekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers for funding the experimental materials and facilities is gratefully acknowledged. The research funding from the Ministry of Science and Higher Education of the Russian Federation (Ural Federal University Program of Development within the Priority–2030 Program) for experiment implementation and analysis of its results is gratefully acknowledged

Manifestation of systemic toxicity in rats after a short-time inhalation of lead oxide nanoparticles

Outbred female rats were exposed to inhalation of lead oxide nanoparticle aerosol produced right then and there at a concentration of 1.30 ± 0.10 mg/m3 during 5 days for 4 h a day in a nose-only setup. A control group of rats were sham-exposed in parallel under similar conditions. Even this short-time exposure of a relatively low level was associated with nanoparticles retention demonstrable by transmission electron microscopy in the lungs and the olfactory brain. Some impairments were found in the organism’s status in the exposed group, some of which might be considered lead-specific toxicological outcomes (in particular, increase in reticulocytes proportion, in δ-aminolevulinic acid (δ-ALA) urine excretion, and the arterial hypertension’s development). © 2020 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was funded by the budget of the Ekaterinburg Medical Research Center for Prophylaxis and Health Protection in Industrial Workers

Biological Prophylaxis in the System of the Management of Occupational Risk Due to Exposure of Metal-Containing Nanoparticles

With taking into account the biological toxicity of metallic and metal oxide nanoparticles to be a well-established fact, the widespread use of nanotechnologies and the significant proportion of nanoscale particles in industrial aerosols released during many pyrometallurgical and electric welding processes determine the importance of searching for approaches to increase the organism's resistance to them. Results of a number of experiments show the application of combinations of some bioactive agents composed in accordance with sound theoretical premises and used in innocuous doses to be potent of the significant attenuation of the integral and specific toxicity of metallic nanoparticles and even their genotoxicity. Further research followed by practical application of the results is a promising trend in the occupational risk management strategy. © СOLLECTIVE OF AUTHORS, 2017

Impact of toxicity effects of zinc oxide nanoparticles in rats within acute and subacute experiments

Introduction. Occupational air is contaminated with zinc oxide nanoparticles in the copper smelting industry, especially in the smelting of brass and copper. A wide range of toxic effects with varied clinical symptomatology is observed in zinc and its compounds. Competitive relations with many other metals, including calcium, copper, and iron, are the foundation of most cases of zinc intoxication. Long-term administration of zinc or its compounds to laboratory rodents affects enzymes, carbohydrates and mineral metabolism. Materials and methods. Subchronic intoxication with repeated intraperitoneal injections and acute low respiratory tract reaction to a single intratracheal injection of zinc nanoparticles were simulated in outbred white rats. Water suspensions of zinc oxide nanoparticles with a 30-80 nm diameter were applied in both experimental models. Upon completion of the exposure, the condition of the rats in all groups was evaluated in many generally accepted criteria for toxicity. The student’s t-test was applied for statistical analysis of the obtained data. Results. Moderate intoxication development in a subchronic experiment is demonstrated. Homogeneous ultrastructural changes in the spleen tissue were revealed. Mitochondrial damage with partial or complete loss of crista is the most common. The fragmentation ratio of DNA was found by a statistically significant increase. A single intratracheal injection of zinc oxide nanoparticles revealed the increase in the attraction of cells capable of their phagocytosis (mainly neutrophils) into the low respiratory tract. This shows their cytotoxicity. Conclusion. Moderate general toxic and cytotoxic effects of zinc oxide nanoparticles on the rat body were identified. © 2021 Izdatel'stvo Meditsina. All rights reserved

Comparative and Combined In Vitro Vasotoxicity of Nanoparticles Containing Lead and Cadmium

In vitro toxicological experiments were performed on an endothelial cell line exposed to different doses of spherical nanoparticles of cadmium and/or of lead sulfides with mean diameter 37 ± 5 nm and 24 ± 4 nm, respectively. Toxic effects were estimated by Luminescent Cell Viability Assay, endothelin-1 concentration and cell size determination. Some dose-response relationships were typically monotonic (well approximated with hyperbolic function) while others were bi- or even 3-phasic and could be described within the expanded hormesis paradigm. The combined toxicity type variated depending on the effect it was assessed by. © The Author(s) 2021

Multisystemic damage to mitochondrial ultrastucture as an integral measure of the comparative in vivo cytotoxicity of metallic nanoparticles

Vehicles emissions of nanoparticles is a one of the major threat to humans in the modern conditions. Subchronic intoxication was induced in outbred male rats by repeated intraperitoneal injections of lead oxide, zinc oxide and copper oxide nanoparticles separately, or in three binary combinations, or in the full triple combination. Based on electron microscopy results, this paper considers the usefulness, feasibility and informativity of an approach based on a generalized semi-quantitative assessment of toxic damage to mitochondria in various organs using partial or complete destruction of cristae as an index of damage. The adequacy of such assessment is confirmed by its consistency with the previously published data on the relative and combined toxicity of nanoparticles of the above species and high protective efficacy of a complex of bioprotectors estimated by a great number of functional and optical-microscopy morphometric indices. © Published under licence by IOP Publishing Ltd

Toxic effects of low-level long-term inhalation exposures of rats to nickel oxide nanoparticles

Rats were exposed to nickel oxide nanoparticles (NiO-NP) inhalation at 0.23 ± 0.01 mg/m3 for 4 h a day 5 times a week for up to 10 months. The rat organism responded to this impact with changes in cytological and some biochemical characteristics of the bronchoalveolar lavage fluid along with a paradoxically little pronounced pulmonary pathology associated with a rather low chronic retention of nanoparticles in the lungs. There were various manifestations of systemic toxicity, including damage to the liver and kidneys; a likely allergic syndrome as indicated by some cytological signs; transient stimulation of erythropoiesis; and penetration of nickel into the brain from the nasal mucous membrane along the olfactory pathway. Against a picture of mild to moderate chronic toxicity of nickel, its in vivo genotoxic effect assessed by the degree of DNA fragmentation in nucleated blood cells (the RAPD test) was pronounced, tending to increasing with the length of the exposure period. When rats were given orally, in parallel with the toxic exposure, a set of innocuous substances with differing mechanisms of expected bioprotective action, the genotoxic effect of NiO-NPs was found to be substantially attenuated. © 2019 by the authors. Licensee MDPI, Basel, Switzerland.For modeling chronic intoxication development under low-level but long-term inhalation exposures to NiO nanoparticles, the experiments were carried out on outbred white female rats from our own breeding colony with an initial body weight of 150–220 g, with a minimum of 12 animals in exposed and control groups. Rats were housed in conventional conditions, breathed unfiltered air, and were fed standard balanced food. The experiments were planned and implemented in accordance with the “International guiding principles for biomedical research involving animals” developed by the Council for International Organizations of Medical Sciences (1985) and were approved by the Ethics Committee of the Ekaterinburg Medical Research Center Medical for Prophylaxis and Health Protection in Industrial Workers