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Neuronal cytotoxicity and genotoxicity induced by zinc oxide nanoparticles
Institution:1. Toxicology Unit, Department of Psychobiology, University of A Coruña, Edificio de Servicios Centrales de Investigación, Campus Elviña s/n, 15071, A Coruña, Spain;2. Clinical and Molecular Epidemiology, IRCCS San Raffaele Pisana, Via di Val Cannuta, 247, 00166, Roma, Italy;3. Department of Environmental Health, Portuguese National Institute of Health, Rua Alexandre Herculano, 321, 4000-055, Porto, Portugal;4. Department of Cell and Molecular Biology, University of A Coruña, Facultad de Ciencias, Campus A Zapateira s/n, 15071, A Coruña, Spain;1. Department of Pharmacognosy, Faculty of Pharmacy, Zabol University of Medical Sciences, Zabol, Iran;2. Department of Plant Breeding and Biotechnology, Faculty of Agriculture, University of Zabol, Zabol, Iran;3. Department of Agriculture, Faculty of Agriculture, University of Zabol, Zabol, Iran;4. Nanobioelectrochemistry Research Center, Bam University of Medical Sciences, Bam, Iran;5. Nanomedicine and Nanobiology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran;6. Student Research Committee, School of Medicine, Bam University of Medical Sciences, Bam, Iran
Abstract:Zinc oxide nanoparticles (ZnO NPs) are one of the most abundantly used nanomaterials in consumer products and biomedical applications. As a result, human exposure to these NPs is highly frequent and they have become an issue of concern to public health. Although toxicity of ZnO NPs has been extensively studied and they have been shown to affect many different cell types and animal systems, there is a significant lack of toxicological data for ZnO NPs on the nervous system, especially for human neuronal cells and tissues. In this study, the cytotoxic and genotoxic effects of ZnO NPs on human SHSY5Y neuronal cells were investigated under different exposure conditions. Results obtained by flow cytometry showed that ZnO NPs do not enter the neuronal cells, but their presence in the medium induced cytotoxicity, including viability decrease, apoptosis and cell cycle alterations, and genotoxicity, including micronuclei production, H2AX phosphorylation and DNA damage, both primary and oxidative, on human neuronal cells in a dose- and time-dependent manner. Free Zn2 + ions released from the ZnO NPs were not responsible for the viability decrease, but their role on other types of cell damage cannot be ruled out. The results obtained in this work contribute to increase the knowledge on the genotoxic and cytotoxic potential of ZnO NPs in general, and specifically on human neuronal cells, but further investigations are required to understand the action mechanism underlying the cytotoxic and genotoxic effects observed.
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