Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Kim, Yong Ho; Fazlollahi, Farnoosh; Kennedy, Ian M.; Yacobi, Nazanin R.; Borok, Zea; Crandall, Edward D.

doi:10.1164/rccm.201002-0185oc

Cited by 93 publications

(58 citation statements)

References 49 publications

(84 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It is well known that ROS can interact with biomolecules including DNA and causes DNA single or double strand breaks and it is also well known that MDA causes free radicals. Some studies have reported similar results (Jeng and Swanson 2006;Musarrat et al 2009;Lin et al 2009;Gerloff et al 2009;Zhu et al 2009;Kim et al 2010). Our findings also clearly demonstrate that ZnO is clastogenic in human lymphocytes in vitro.…”

Section: Discussionsupporting

confidence: 89%

In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

et al. 2013

View full text Add to dashboard Cite

In this study, possible genotoxic effects of zinc oxide (ZnO) nanoparticles were investigated in cultured human peripheral lymphocytes by using chromosome aberrations and micronucleus assays (MN). For this purpose, the cells were treated with ZnO (1, 2, 5, 10, 15 and 20 lg/mL) for 24 and 48 h. In this research, four types of chromosome aberrations were observed as chromatid and chromosome breaks, fragment and dicentric chromosomes. ZnO induced significant increase of the ratio of chromosomal aberrations as well as percentage of abnormal cells at concentrations of 1, 5, 10 and 20 lg/mL in 24 h treatments. In 48 h treatments, while ZnO nanomaterials induced significant increase of the percentage of abnormal cells only at a concentration of 10 lg/mL, and of chromosome aberration per cell in comparison to the control at concentrations of 5 and 10 lg/mL. On the other hand, this material significantly increased the micronuclei frequency (MN) at concentrations of 10 and 15 lg/mL in comparison to the control. Cytokinesis-block proliferation index was not affected by ZnO treatments. It also decreased the mitotic index in all concentrations at 24 h but not at 48 h. The present results indicate that ZnO nanoparticles are clastogenic, mutagenic and cytotoxic to human lymphocytes in vitro at specific concentrations and time periods.

show abstract

Section: Discussionsupporting

confidence: 89%

In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

et al. 2013

View full text Add to dashboard Cite

show abstract

“…38 Mitochondrial activity was decreased, while LDH release and intracellular ROS were increased. Tight junctions were disrupted.…”

Section: +mentioning

confidence: 97%

A review of mammalian toxicity of ZnO nanoparticles

Vandebriel¹,

Jong²

2012

NSA

434

247

View full text Add to dashboard Cite

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.

show abstract

“…Also, Kim et al (2010) exposed primary cultured rat alveolar epithelial cell monolayers to ZnO NPs and observed injury of the cells in dose-and time-dependent manner caused at least partially by free Zn ions released from ZnO NPs, mitochondrial dysfunction and increased intracellular ROS.…”

Section: Oxidative Stress and The Related Effects Of Nanoparticlesmentioning

confidence: 99%

Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: A comparative review

et al. 2013

View full text Add to dashboard Cite

Silver, ZnO and CuO nanoparticles (NPs) are increasingly used as biocides. There is however increasing evidence of their threat to ''non-target'' organisms. In such a context, the understanding of the toxicity mechanisms is crucial for both the design of more efficient nanoantimicrobials, i.e. for ''toxic by design'' and at the same time for the design of nanomaterials that are biologically and/or environmentally benign throughout their life-cycle (safe by design). This review provides a comprehensive and critical literature overview on Ag, ZnO and CuO NPs' toxicity mechanisms on the basis of various environmentally relevant test species and mammalian cells in vitro. In addition, factors modifying the toxic effect of nanoparticles, e.g. impact of the test media, are discussed. Literature analysis revealed three major phenomena driving the toxicity of these nanoparticles: (i) dissolution of nanoparticles, (ii) organismdependent cellular uptake of NPs and (iii) induction of oxidative stress and consequent cellular damages. The emerging information on quantitative structure-activity relationship modeling of nanomaterials' toxic effects and the challenges of extrapolation of laboratory results to the environment are also addressed.

show abstract

Alveolar Epithelial Cell Injury Due to Zinc Oxide Nanoparticle Exposure

Cited by 93 publications

References 49 publications

In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

In vitro genotoxic effects of ZnO nanomaterials in human peripheral lymphocytes

A review of mammalian toxicity of ZnO nanoparticles

Mechanisms of toxic action of Ag, ZnO and CuO nanoparticles to selected ecotoxicological test organisms and mammalian cells in vitro: A comparative review

Contact Info

Product

Resources

About