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Cytotoxicity of zinc oxide (nano)particles in a rat intestinal cell model: effect on cellular glutathione and mitochondria
Citation:
Henson, T., J. Navratilova, K. Bradham, A. Tennant, K. Rogers, AND M. Hughes. Cytotoxicity of zinc oxide (nano)particles in a rat intestinal cell model: effect on cellular glutathione and mitochondria. Society of Toxicology, Anaheim, California, March 15 - 19, 2020. https://doi.org/10.23645/epacomptox.18737387
Impact/Purpose:
Poster presented to the Society of Toxicology (SOT) meeting March 2020. Human exposure to zinc oxide nanoparticles (ZnO NPs) may occur by the oral route. In this study we examined ZnO NPs cytotoxicity in a rat intestinal cell model and assessed mitochondrial health and cellular glutathione levels. The size of the particles were of 10 and 150 nm. We also examined dissolution of the particles in media. Both mitochondrial health and glutathione concentrations were affected by both particles in a dose-dependent manner after a 4 hour exposure. model. The results suggest that ZnO NPs of both sizes dissolve to zinc ions, which elicit a cytotoxic response.
Description:
Zinc oxide nanoparticles (NPs) have a variety of commercial and biomedical applications ranging from UV filtration in sunscreen to anti-cancer, fungal and anti-microbial agents. Human oral exposure to zinc oxide NPs may occur following accidental or intentional ingestion, hand-to-mouth activity, or mucociliary transport following inhalation. This study assessed the cytotoxicity of two different sized zinc oxide particles (10 and 150 nm) in rat intestinal cells (IEC-6). The 10 nm particle is classified as a nanoparticle. Previously we have reported that the cytotoxicity of these two particles and zinc ions are time- and dose-dependent in these cells. Dissolution of the particles and ZnSO4 in media with 10% serum protein was assessed over 24 h. Zn concentration in incubation filtrate was determined by ICP-OES and was assumed to be free zinc ion. Intracellular glutathione (GSH) concentrations and mitochondrial area were assessed in the IEC-6 cells using spectroscopic methods after a 4-h exposure to the particles (0.1 – 100 ug/mL) or ZnSO4 (100 ug/mL). Dissolution studies in media showed that both particles formed soluble Zn ions, and that media components bind these ions. At 24 h, approximately 40% of ZnSO4, 40% of 10 nm ZnO and 30% of 150 nm ZnO was detected as free Zn ion in the filtrate. In H2O, 100% ZnSO4 was detected in filtrate at 24 h, showing complete dissolution. A significant dose-dependent decrease in cellular GSH and mitochondrial area was detected in the IEC-6 cells after a 4-h exposure to both particles and ZnSO4. Both cellular GSH and mitochondrial area in treated cells decreased up to 40% relative to non-treated cells. The results suggest that ZnO particles, regardless of size, form zinc ions in media. Decreased cellular GSH may result from the reaction of this thiol with reactive oxygen species, which may be formed by zinc ions. The increased oxidative stress in the treated cells may also be damaging to the mitochondria. An imbalance of a cellular antioxidant such as GSH caused indirectly by zinc ions formed from ZnO particles may result in impairment of organelles such as the mitochondria resulting in cell death.
URLs/Downloads:
DOI: Cytotoxicity of zinc oxide (nano)particles in a rat intestinal cell model: effect on cellular glutathione and mitochondria
HENSON_SOT 2020_V3.PDF (PDF, NA pp, 2597.002 KB, about PDF)