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

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

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