Some Peculiarities in the Dose Dependence of Separate and Combined In Vitro Cardiotoxicity Effects Induced by CdS and PbS Nanoparticles With Special Attention to Hormesis Manifestations

Spherical nanoparticles (NPs) of cadmium and lead sulfides (diameter 37 ± 5 and 24 ± 4 nm, respectively) have been found to be cytotoxic for HL-1 cardiomyocytes as evidenced by decrease in adenosine triphosphate–dependent luminescence. Cadmium sulfide (CdS)-NPs were discovered to produce a much greater cytotoxic impact than lead sulphide (PbS)-NP. Given the same dose range, CdS-NP reduced the number of calcium spikes. A similar effect was observed for small doses of PbS-NP. In addition to cell hypertrophy under the impact of certain doses of CdS-NP and PbS-NP, doses causing cardiomyocyte size reduction were identified. For these 3 outcomes, we obtained both monotonic “dose–response” functions (well approximated by the hyperbolic function) and different variants of non-monotonic ones for which we found adequate mathematical expressions by modifying certain models of hormesis available in the literature. Data analysis using a response surface linear model with a cross-term provided new support to the previously established postulate that a diversity of types of joint action characteristic of one and the same pair of damaging agents is one of the important assertions of the general theory of combined toxicity. © The Author(s) 2020

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

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

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

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

New Data on Variously Directed Dose-Response Relationships and the Combined Action Types for Different Outcomes of in Vitro Nanoparticle Cytotoxicity

Spherical selenium-oxide and copper-oxide nanoparticles (SeO-NP with mean diameter 51 ± 14 nm and CuO-NP with mean diameter 21 ± 4 nm) were found to be cytotoxic for human fibroblast-like cells in vitro, as judged by decreased ATP-dependent luminescence. Compared with SeO-NP, CuO-NP produced a somewhat stronger effect of this kind. Along with cell hypertrophy developing in response to certain doses of SeO-NP and CuO-NP, our experiment also revealed doses causing a decrease in cell and cell-nucleus sizes. We observed both monotonic and different variants of nonmonotonic dose-response relationship. For the latter, we have succeeded in constructing adequate mathematical expressions based on the generalized hormesis paradigm that we had considered previously in respect of CdS-NP and PbS-NP cytotoxicity for cardiomyocites. It was demonstrated as well that combined toxicity of SeO-NP and CuO-NP is of different types depending on the outcome. © The Author(s) 2021.The author(s) received no financial support for the research, authorship, and/or publication of this article. The equipment of the Ural Center for Shared Use "Modern nanotechnology" Ural Federal University (Reg.& numero; 2968) was used

Type 1 Diabetes Impairs Cardiomyocyte Contractility in the Left and Right Ventricular Free Walls but Preserves It in the Interventricular Septum

Type 1 diabetes (T1D) leads to ischemic heart disease and diabetic cardiomyopathy. We tested the hypothesis that T1D differently affects the contractile function of the left and right ventricular free walls (LV, RV) and the interventricular septum (IS) using a rat model of alloxan-induced T1D. Single-myocyte mechanics and cytosolic Ca2+ concentration transients were studied on cardiomyocytes (CM) from LV, RV, and IS in the absence and presence of mechanical load. In addition, we analyzed the phosphorylation level of sarcomeric proteins and the characteristics of the actin-myosin interaction. T1D similarly affected the characteristics of actin-myosin interaction in all studied regions, decreasing the sliding velocity of native thin filaments over myosin in an in vitro motility assay and its Ca2+ sensitivity. A decrease in the thin-filament velocity was associated with increased expression of β-myosin heavy-chain isoform. However, changes in the mechanical function of single ventricular CM induced by T1D were different. T1D depressed the contractility of CM from LV and RV; it decreased the auxotonic tension amplitude and the slope of the active tension-length relationship. Nevertheless, the contractile function of CM from IS was principally preserved. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.Funding: This work was supported by the Russian Science Foundation № 18-74-10059. The work was performed using the equipment of the Shared Research Center of Scientific Equipment of Institute of Immunology and Physiology