Toxicological effects of selenium nanoparticles in laboratory animals: A review.

This paper provides a comprehensive summary of the main toxicological studies conducted on selenium nanoparticles (NPs) using laboratory animals, up until February 28, 2023. A literature search revealed 17 articles describing experimental studies conducted on warm-blooded animals. Despite some uncertainties, in vivo studies have demonstrated that selenium NPs have an adverse effect on laboratory animals, as evidenced by several indicators of general toxic action. These effects include reductions of body mass, changes in hepatotoxicity indices (increased enzyme activity and accumulation of selenium in the liver), and the possibility of impairment of fatty acid, protein, lipid, and carbohydrate metabolisms. However, no specific toxic action attributable solely to selenium has been identified. The LOAEL and NOAEL values are contradictory. The NOAEL was 0.22 mg/kg body weight per day for males and 0.33 mg/kg body weight per day for females, while the LOAEL was assumed to be a dose of 0.05 mg/kg of nanoselenium. This LOAEL value is much higher for rats than for humans. The relationship between the adverse effects of selenium NPs and exposure dose is controversial and presents a wide typological diversity. Further research is needed to clarify the absorption, metabolism, and long-term toxicity of selenium NPs, which is critical to improving the risk assessment of these compounds.

On the Mechanisms of the Cardiotoxic Effect of Lead Oxide Nanoparticles.

Lead compounds are one of the most common pollutants of the workplace air and the environment. In the occupational setting, the sources of their emission, including in nanoscale form, are various technological processes associated with lead smelting and handling of non-ferrous metals and their alloys, the production of copper and batteries. Both lead poisoning and lead exposure without obvious signs of poisoning have a detrimental effect on the cardiovascular system. The purpose of this research was to investigate the mechanisms of the cardiotoxic effect of lead oxide nanoparticles (PbO NPs). The toxicological experiment involved male albino rats subchronically exposed to PbO NPs (49.6 ± 16.0 nm in size) instilled intraperitoneally in a suspension. We then assessed post-exposure hematological and biochemical parameters of blood and urine, histological and ultrastructural changes in cardiomyocytes, and non-invasively recorded electrocardiograms and blood pressure parameters in the rodents. Myocardial contractility was studied on isolated preparations of cardiac muscles. We established that PbO NPs induced oxidative stress and damage to the ultrastructure of cardiomyocytes, and decreased efficiency of the contractile function of the myocardium and blood pressure parameters. We also revealed such specific changes in the organism of the exposed rats as anemia, hypoxia, and hypocalcemia.

Toxic Kidney Damage in Rats Following Subchronic Intraperitoneal Exposure to Element Oxide Nanoparticles.

Chronic diseases of the urogenital tract, such as bladder cancer, prostate cancer, reproductive disorders, and nephropathies, can develop under the effects of chemical hazards in the working environment. In this respect, nanosized particles generated as by-products in many industrial processes seem to be particularly dangerous to organs such as the testes and the kidneys. Nephrotoxicity of element oxide particles has been studied in animal experiments with repeated intraperitoneal injections of Al2O3, TiO2, SiO2, PbO, CdO, CuO, and SeO nanoparticles (NPs) in total doses ranging from 4.5 to 45 mg/kg body weight of rats. NPs were synthesized by laser ablation. After cessation of exposure, we measured kidney weight and analyzed selected biochemical parameters in blood and urine, characterizing the state of the excretory system. We also examined histological sections of kidneys and estimated proportions of different cells in imprint smears of this organ. All element oxide NPs under investigation demonstrated a nephrotoxic effect following subchronic exposure. Following the exposure to SeO and SiO2 NPs, we observed a decrease in serum creatinine and urea, respectively. Exposure to Al2O3 NPs caused an increase in urinary creatinine and urea, while changes in total protein were controversial, as it increased under the effect of Al2O3 NPs and was reduced after exposure to CuO NPs. Histomorphological changes in kidneys are associated with desquamation of the epithelium (following the exposure to all NPs except those of Al2O3 and SiO2) and loss of the brush border (following the exposure to all NPs, except those of Al2O3, TiO2, and SiO2). The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. Compared to the controls, we observed statistically significant alterations in 42.1% (8 of 19) of parameters following the exposure to PbO, CuO, and SeO NPs in 21.1% (4 of 19)-following that, to CdO and Al2O3 NPs-and in 15.8% (3 of 19) and 10.5% (2 of 19) of indicators, following the exposure to TiO2 and SiO2 nanoparticles, respectively. Histomorphological changes in kidneys are associated with desquamation of epithelium and loss of the brush border. The cytomorphological evaluation showed greater destruction of proximal sections of renal tubules. The severity of cyto- and histological structural changes in kidneys depends on the chemical nature of NPs. These alterations are not always consistent with biochemical ones, thus impeding early clinical diagnosis of renal damage. Unambiguous ranking of the NPs examined by the degree of their nephrotoxicity is difficult. Additional studies are necessary to establish key indicators of the nephrotoxic effect, which can facilitate early diagnosis of occupational and nonoccupational nephropathies.

Features of the response to subchronic low-dose exposure to copper oxide nanoparticles in rats.

Copper is an essential trace element for human health and, at the same time, a major industrial metal widely used both in its elemental form and in compounds. We conducted a dose-dependent assessment of the response of outbred albino male rats to subchronic low-dose exposure to copper oxide nanoparticles administered intraperitoneally at cumulative doses of 18 and 36 mg/kg during 6 weeks to exposure groups 1 and 2, respectively. We observed disorders at different levels of organization of the body in the exposed animals, from molecular to organismal. The observed decrease in the activity of succinate dehydrogenase in nucleated blood cells gave evidence of impaired bioenergetics processes. In view of the results of the metabolomics analysis, we assume mitochondrial damage and contribution of apoptotic processes to the pathology induced by copper poisoning. We also assume neurodegenerative effects based on the assessed morphological parameters of the nervous system, results of behavioral tests, and a decreased level of expression of genes encoding NMDA receptor subunits in the hippocampus. The hepatotoxic effect noted by a number of metabolomics-based, biochemical, and cytological indicators was manifested by the impaired protein-synthesizing function of the liver and enhanced degenerative processes in its cells. We also observed a nephrotoxic effect of nanosized copper oxide with a predominant lesion of proximal kidney tubules. At the same time, both doses tested demonstrated such positive health effects as a statistically significant decrease in the activity of alkaline phosphatase and the nucleated blood cell DNA fragmentation factor. Judging by the changes observed, the cumulative dose of copper oxide nanoparticles of 18 mg/kg body weight administered intraperitoneally approximates the threshold one for rats. The established markers of health impairments may serve as a starting point in the development of techniques of early diagnosis of copper poisoning.

Comparative Evaluation of the Cytotoxic Effects of Metal Oxide and Metalloid Oxide Nanoparticles: An Experimental Study.

Industrial production generates aerosols of complex composition, including an ultrafine fraction. This is typical for mining and metallurgical industries, welding processes, and the production and recycling of electronics, batteries, etc. Since nano-sized particles are the most dangerous component of inhaled air, in this study we aimed to establish the impact of the chemical nature and dose of nanoparticles on their cytotoxicity. Suspensions of CuO, PbO, CdO, Fe2O3, NiO, SiO2, Mn3O4, and SeO nanoparticles were obtained by laser ablation. The experiments were conducted on outbred female albino rats. We carried out four series of a single intratracheal instillation of nanoparticles of different chemical natures at doses ranging from 0.2 to 0.5 mg per animal. Bronchoalveolar lavage was taken 24 h after the injection to assess its cytological and biochemical parameters. At a dose of 0.5 mg per animal, cytotoxicity in the series of nanoparticles changed as follows (in decreasing order): CuO NPs > PbO NPs > CdO NPs > NiO NPs > SiO2 NPs > Fe2O3 NPs. At a lower dose of 0.25 mg per animal, we observed a different pattern of cytotoxicity of the element oxides under study: NiO NPs > Mn3O4 NPs > CuO NPs > SeO NPs. We established that the cytotoxicity increased non-linearly with the increase in the dose of nanoparticles of the same chemical element (from 0 to 0.5 mg per animal). An increase in the levels of intracellular enzymes (amylase, AST, ALT, LDH) in the supernatant of the bronchoalveolar lavage fluid indicated a cytotoxic effect of nanoparticles. Thus, alterations in the cytological parameters of the bronchoalveolar lavage and the biochemical characteristics of the supernatant can be used to predict the danger of new nanomaterials based on their comparative assessment with the available tested samples of nanoparticles.

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.

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.