Features of toxic effect due to biodistribution and bio-accumulation of nano- and microparticles of copper (II) oxide

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Abstract

Introduction. With the expansion of the range of applications of copper oxide nanoparticles (CuO NPs) in various fields of economic activity, the risk of exposure of the population and workers to nanomaterials increases. The physicochemical properties of NPs, differed from microparticles (MPs) of a chemical analogue, may determine the development of more pronounced negative effects associated with exposure to nanomaterials. In this regard, to increase the effectiveness of preventive measures, there is needed research aimed at studying and clarifying the pathogenetic features of the toxicity of CuO NPs, other than MPs, under their long-term entering the body through various routes.
The aim of the study. To characterise of the toxic effects of CuO NPs and MPs caused by their biodistribution and bio-accumulation during chronic inhalation exposure in an experiment.
Materials and methods. The physical properties of CuO NPs were studied in comparison with MPs. In a chronic inhalation experiment on Wistar rats, the features of bioaccumulation and morphofunctional disorders caused by CuO NPs when exposed to a concentration of 0.012 mg/m3 for 180 days, distinctive from MPs, were studied and identified.
Results. CuO NPs, in comparison with MPs, have a smaller size (by 305 times), a larger specific surface area (by 9.6 times) and a total pore volume (9.3 times), which determines the greater penetrating ability of NPs. CuO NPs have a more pronounced biodistribution compared to MPs, which is noted by the number of organs with an increased concentration of the substance (with exposure to NPs – in the lungs, live,r and kidneys, by 1.43–2.29 times higher relative to the control; with MPs exposure – in the lungs, by 1.35 times). NPs have a more pronounced degree of bio-accumulation in the lungs, liver, and kidneys (1.43–2.32 times) compared to MPs. Exposure to CuO NPs causes changes in indicators of negative effects characteristic of the activation of the oxidative process (increase in MDA activity, decrease in AOA by 1.29–1.96 times relative to the control), inflammatory response (increase in the concentration of С-reactive protein (CRP) and the number of leukocytes by 1.8 times), impaired liver function (decrease urea content by 1.53 times), cytotolysis (increase in the activity of LDH, ALT, AST by 1.81–2.39 times). When exposed to MPs, the oxidative process, inflammation, and cytolysis were also noted, but the degree of changes in their parameters was 1.30–1.79 times less pronounced. When exposed to NPs in the lung tissues of rats, an abscess, pneumonia, bronchitis, vasculitis, and plethora develop; liver tissues – hepatitis, plethora; kidney tissues – proliferation of mesangial cells. In rats exposed to MPs, only hyperplasia of the peribronchial lymph nodes in the lungs was noted.
Limitations. The study was carried out only with chronic inhalation exposure to CuO NPs and MPs on Wistar rats.
Conclusion. CuO NPs have more pronounced biodistribution and bio-accumulation, which causes a greater spectrum and degree of manifestation of negative effects (activation of the oxidative process, inflammatory response, impaired liver function, cytolysis, pathomorphological changes in lungs, liver and kidney tissues) in comparison with the microsized chemical analogue. It is advisable to take into account the results obtained to increase the effectiveness of scientifically based recommendations aimed at preventing and minimizing negative effects in humans that arise from exposure to CuO NPs in the processes of production, consumption, and utilization of products containing them.

About the authors

Marina A. Zemlyanova

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies; Perm State National Research University

Author for correspondence.
Email: zem@fcrisk.ru
ORCID iD: 0000-0002-8013-9613
Russian Federation

Mark S. Stepankov

Federal Scientific Center for Medical and Preventive Health Risk Management Technologies

Email: stepankov@fcrisk.ru
ORCID iD: 0000-0002-7226-7682
Russian Federation

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