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Cytotoxicity of copper (II) oxide nanoparticles in rat and human intestinal cell models
Citation:
Henson, T., J. Navratilova, J. Griggs, K. Bradham, K. Rogers, AND M. Hughes. Cytotoxicity of copper (II) oxide nanoparticles in rat and human intestinal cell models. Society of Toxicology, Baltimore, Maryland, March 12 - 16, 2017.
Impact/Purpose:
There is a potential for human oral exposure to copper (II) oxide nanoparticles following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. The objective of this study was to assess the cytotoxic effects of copper oxide nanoparticles (size <50 nm) in rat and human intestinal cells.
Description:
CuO nanoparticles (NPs) have a variety of commercial applications ranging from catalysts to semiconductors. There is a potential for human oral exposure to CuO NPs following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. The objective of this study was to assess the cytotoxic effects of CuO NPs (size <50 nm) in rat and human intestinal cells. The rat cells are a 2-dimensional model (IEC-6) while the human cells are a 3-dimensional highly differentiated intestinal model. The effect of dose (0.1 – 100 ug/ml rat; 1-100 ug/ml, human) and time (4 and 24 h) were evaluated. Cytotoxicity was assessed using a colorimetric method that measures mitochondrial activity (MTS, rat; MTT, human). Media with 10% fetal bovine serum was used as the negative control and triton X-100 (0.3%) was the positive control. CuSO4 (0.1 – 100 ug/ml) was also tested in the rat cells for 24 h to assess Cu ion toxicity. Nanoparticles were suspended in media and probe sonicated before dosing. Following incubation, the cells were washed with saline. In the rat cells, a significant dose-dependent (p<0.0001) decrease in cell viability was observed after 4- and 24-h incubation of the CuO NPs. For both time points, a significant decrease was detected at ≥ 5 ug/ml CuO NPs in the rat cells. In the human cells, a significant dose-dependent (p<0.0001) decrease in cell viability was observed only after a 24-h incubation of the CuO NPs; a significant decrease was detected at ≥ 50 ug/ml CuO NPs. Comparison of CuSO4 vs. CuO NPs in rat cells showed greater cytotoxicity of the NPs, suggesting toxicity of the NPs is not due to release of Cu ions alone. Transmission electron microscopy of the CuO NPs in media showed CuO NP aggregates measuring <3 µm. CuO NPs are cytotoxic to rat and human intestinal cells in a dose- and time-dependent manner, although the rat model appears to be more sensitive. The 3-dimensional human model may be able to limit absorption of the CuO NPs or is better able to repair damage induced by these particles.