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In vitro intestinal toxicity of copper nanoparticles in rat and human cell models
Citation:
Hughes, M., T. Henson, J. Navaratilova, A. Tennant, K. Bradham, AND K. Rogers. In vitro intestinal toxicity of copper nanoparticles in rat and human cell models. QEEM II: 2nd Quantifying Exposure to Engineered Nanomaterials from Manufactured Products Workshop, Washington, DC, Washington, DC, October 09 - 10, 2018.
Impact/Purpose:
The purpose of this study was to asses the cytotoxicity of CuO and Cu2O-polyvinylpyrrolidone (PVP) coated NPs and Cu2+ ions in rat (IEC-6) and human intestinal cells, two- and three-dimensional models, respectively.
Description:
Human oral exposure to copper oxide nanoparticles (NPs) may occur following ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxicity of CuO and Cu2O-polyvinylpyrrolidone (PVP) coated NPs and Cu2+ ions in rat (IEC-6) and human intestinal cells, two- and three-dimensional models, respectively. The effect of pre-treatment of CuO NPs with simulated gastrointestinal (GI) fluids on IEC-6 cell cytotoxicity was also investigated. Both dose- and time-dependent decreases in viability of rat and human cells with CuO and Cu2O-PVP NPs and Cu2+ ions was observed. In the rat cells, CuO NPs had greater cytotoxicity. The rat cells were also more sensitive to CuO NPs than the human cells. Concentrations of H2O2 and glutathione increased and decreased, respectively, in IEC-6 cells after a 4-h exposure to CuO NPs, suggesting formation of reactive oxygen species (ROS). These ROS may have damaged the mitochondrial membrane of the IEC-6 cells causing a depolarization, as a dose-related loss of a fluorescent mitochondrial marker was observed following a 4-h exposure to CuO NPs. Dissolution studies showed that Cu2O-PVP NPs formed soluble Cu whereas CuO NPs essentially remained intact. For GI fluid-treated CuO NPs, there was a slight increase in cytotoxicity at low doses relative to non-treated NPs. In summary, copper oxide NPs were cytotoxic to rat and human intestinal cells in a dose- and time-dependent manner. The data suggests CuO NPs have inherent cytotoxicity, without dissolving and forming toxic Cu2+ ions, whereas Cu2O-PVP NPs are toxic due to their dissolution to these ions. (This abstract does not represent US EPA policy.)