A review of mammalian toxicity of ZnO nanoparticles

Abstract

This review summarizes the literature on mammalian toxicity of ZnO nanoparticles (NPs) published between 2009 and 2011. The toxic effects of ZnO NPs are due to the compound's solubility. Whether the increased intracellular [Zn 2+ ] is due to the NPs being taken up by cells or to NP dissolution in medium is still unclear. In vivo airway exposure poses an important hazard. Inhalation or instillation of the NPs results in lung inflammation and systemic toxicity. Reactive oxygen species (ROS) generation likely plays an important role in the inflammatory response. The NPs do not, or only to a minimal extent, cross the skin; this also holds for sunburned skin. Intraperitoneal administration induces neurological effects. The NPs show systemic distribution; target organs are liver, spleen, lung, and kidney and, in some cases, the heart. In vitro exposure of BEAS-2B bronchial epithelial cells and A549 alveolar adenocarcinoma cells results in cytotoxicity, increased oxidative stress, increased intracellular [Ca 2+ ], decreased mitochondrial membrane potential, and interleukin (IL)-8 production. Decreased contractility of airway smooth muscle cells poses an additional hazard. In contrast to the results for BEAS-2B and A549 cells, in RKO colon carcinoma cells ZnO NPs and not Zn 2+ induce cytotoxicity and mitochondrial dysfunction. Short-term exposure of skin cells results in apoptosis but not in an inflammatory response, while long-term exposure leads to increased ROS generation, decreased mitochondrial activity, and formation of tubular intercellular structures. Macrophages, monocytes, and dendritic cells are affected; exposure results in cytotoxicity, oxidative stress, intracellular Ca 2+ flux, decreased mitochondrial membrane potential, and production of IL-1β and chemokine CXCL9. The NPs are phagocytosed by macrophages and dissolved in lysosomes. In vitro the Comet assay and the cytokinesis-blocked micronucleus assay show genotoxicity, whereas the Ames test does not. This is, however, not confirmed by in vivo genotoxicity assays. Protein binding results in increased stability.

The potentiation effect makes the difference: Non-toxic concentrations of ZnO nanoparticles enhance Cu nanoparticle toxicity in vitro

“…Here, addition of ZnONPs with the largest size (57 nm) to CuNPs caused the highest cytotoxicity in HepG2 cells. These findings are in agreement with the idea that the interaction of large ZnONPs aggregates with the membrane is one of the factors driving toxicity (Vakurov et al, 2013;Vandebriel and De Jong, 2012). Moreover, they indicate that the exposure of cells to combinations of NPs introduces new factors that greatly contribute to determining the global toxicity of the mixture.…”

Comparative Proteomic Analysis of Rat Bronchoalveolar Lavage Fluid after Exposure to Zinc Oxide Nanoparticles

“…Although the antioxidantrelated proteins that reported by Fukui et al (including lipid peroxide, heme oxygenase-1 and alpha-tocopherol) 8) were not identi ed in our study, the other similar antioxidant proteins, peroxiredoxin-6 and -1, were observed with up-regulation in BALF of ZnO NPs exposed rats (Table 1). According to the above observations, these ndings support those reported previously, 1,6) namely that inhalation or instillation of ZnO NPs predominantly results in lung in ammation and systemic toxicity.…”

“…1) As a result of all these uses, it is therefore necessary to provide a complete understanding of ZnO NPs toxicity.…”

“…[3][4][5] Furthermore, there have been an increasing number of studies demonstrated that ZnO NPs can induce lung and systemic immunomodulatory consequences in human and animal systems. 1,6) For example, Roy et al showed the ZnO NPs provided an adjuvant e ect and induced 2 responses in mice exposed to the allergen ovalbumin 7) ; Fukui et al reported the intratracheal instillation of ZnO NPs can induce an increase in antioxidants, including lipid peroxide, heme oxygenase-1 and alpha-tocopherol, in the lungs of exposed rat. 8) Moreover, a previous study found that ZnO NPs were highest potency regarding induction of acute lung in ammation in murine inhalation model.…”

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“…ZnO NPs are widely used in several applications including cosmetics, plastic, paints, as drug carriers, UV-stabilizer, environ mental remediat ion, wastewater treatment and fillings in medical materials (Dufour, Ku maravel, Nohynek, Kirkland, & Toutain, 2006;Vandebriel & De Jong, 2012). For Eu rope and the U.S., total concentrations of ZnO NPs in surface waters were reported as 0.010 (0.008-0.055) µg/l and 0.001 (0.001-0.003) µg/l, respectively (Gottschalk, Sonderer, Scholz, & Nowack, 2009).…”