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Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro

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Abstract

Heavy metals are found naturally on Earth and exposure to them in the living environment is increasing as a consequence of human activity. The toxicity of six different metal oxide nanoparticles (NP) at different points in time was compared using resazurin assay. After incubating Caco2 and A549 cells with 100 μg/mL of Sb2O3, Mn3O4 and TiO2 nanoparticles (NPs) for 24 h no toxic effects were observed while Co3O4 and ZnO NPs had moderate effects and CuO NPs were toxic below 100 μg/mL (24 h EC25 = 11 for A549 and 71 μg/mL for Caco2). The long-term monitoring (up to 9 days) of cells to NPs revealed that the toxic effects of Mn3O4 and Sb2O3 NPs remarkably increased over time. The 9 day EC50 values for Sb2O3 NPs were 22 and 48 μg/mL for A549 and Caco2 cells; and for Mn3O4 NPs were 47 and 29 μg/mL for A549 and Caco2 cells, respectively. In general, the sensitivity of the cell lines in the resazurin assay was comparable. Trans epithelial electrical resistance (TEER) measurements were performed for both cell types exposed to Co3O4, Sb2O3 and CuO NPs. In TEER assay, the Caco2 cells were more susceptible to the toxic effects of these NPs than A549 cells, where the most toxic NPs were the Sb2O3 NPs: the permeability of the Caco2 cell layer exposed to 10 μg/mL Sb2O3 NPs already increased after 24 h of exposure.

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Acknowledgments

This research was supported by the EU FP7 Project MODERN under Grant Agreement No. 309314, SA Archimedes project Functional Food Ingredients, and Tallinn University Centre of Excellence “Natural sciences and sustainable development” and Estonian Institutional research funding project IUT 23-5. Thanks also go to Dr. Suman Pokhrel (University of Bremen, Germany) for providing the Co3O4, CuO, Mn3O4, Sb2O3, ZnO and TiO2 NPs. Thanks to Dr. Meeri Visnapuu (NICPB, Tartu University, Estonia) for TEM photographs. Thanks also go to Finnish Centre for Alternative Methods (FICAM, Tampere) for providing the Balb/c 3T3 cell line (ATCC CCL-163).

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Titma, T., Shimmo, R., Siigur, J. et al. Toxicity of antimony, copper, cobalt, manganese, titanium and zinc oxide nanoparticles for the alveolar and intestinal epithelial barrier cells in vitro. Cytotechnology 68, 2363–2377 (2016). https://doi.org/10.1007/s10616-016-0032-9

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