In vitro intestinal toxicity of copper oxide nanoparticles in rat and human cell models. Issue 6 (3rd July 2019)

• Record Type: Journal Article
• Authors: Henson, Taylor E.; Navratilova, Jana; Tennant, Alan H.; Bradham, Karen D.; Rogers, Kim R.; Hughes, Michael F.
• Is Part Of: Nanotoxicology. Volume 13:Issue 6(2019)
• Page Start: 795
• Page End: 811
• Publication Date: 2019-07-03
• Subjects: Intestine -- nanoparticles -- copper oxide -- in vitro -- toxicity -- reactive oxygen species; Toxicology -- Periodicals; 615.9
• DOI: 10.1080/17435390.2019.1578428
• Languages: English
• ISSNs: 1743-5390

Abstract

Abstract: 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 Cupric (II) oxide (CuO) and Cu2 O-polyvinylpyrrolidone (PVP) coated NPs and copper ions in rat (intestine epithelial cells; IEC-6) and human intestinal cells, two- and three-dimensional models, respectively. The effect of pretreatment 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 Cu2 O-PVP NPs and Cu 2+ 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 H2 O2 and glutathione increased and decreased, respectively, in IEC-6 cells after a 4-h exposure to CuO NPs, suggesting the 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 Cu2 O-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 Cu2 O-PVP NPs are toxic due to their dissolution to Cu ions, whereas CuO NPs have inherent cytotoxicity, without dissolving to form Cu ions.