Cytotoxicity and global transcriptional responses induced by zinc oxide nanoparticles NM 110 in PMA-differentiated THP-1 cells

Safar, Ramia; Doumandji, Zahra; Saidou, Timeh; Ferrari, Luc; Nahle, Sara; Rihn, Bertrand; Joubert, O.

doi:10.1016/j.toxlet.2018.11.003

Cited by 33 publications

(22 citation statements)

References 32 publications

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“…Here, in our experimental conditions, we showed that ZnO NPs display the larger primary size and the lower specific area, suggesting that ZnO toxicity in this model could be attributed to other properties such as their solubility, morphology, or presence of Zn. Our data are in agreement with the reported toxicity of ZnO in rat epithelial and pulmonary cell models as well as in in PMAdifferentiated THP-1 monocytic cells to a macrophagelike phenotype (Safar et al 2018;Wiemann et al 2016). Moreover, the ZnO NPs toxicity potential seems to be cell-type dependent as similar concentrations of ZnO NPs do not lead to any cytotoxicity in exposed human monocyte THP1 cells and in human umbilical vein endothelial cells (Chen et al 2017;Gong et al 2017).…”

Section: Discussionsupporting

confidence: 91%

“…Our results are in agreement with those of Tuomela et al (2013) who demonstrated an overexpression of different metallothioneins as a gene signature of three different immune cell lines after the exposure to ZnO NPs. Other recent studies revealed as well the expression of MTs after exposure to Zn, nano-ZnO, or micro-ZnO (Chai et al 2014;Safar et al 2018;Yang et al 2017). The overexpression of metallothioneins is an indicator of an adaptive response that plays a role in defense mechanisms against oxidative stress.…”

Section: Discussionmentioning

confidence: 96%

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Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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Metal oxide nanoparticles (NPs), such as ZnO, ZnFe 2 O 4 , and Fe 2 O 3 , are widely used in industry. However, little is known about the cellular pathways involved in their potential toxicity. Here, we particularly investigated the key molecular pathways that are switched on after exposure to sub-toxic doses of ZnO, ZnFe 2 O 4 , and Fe 2 O 3 in the in vitro rat alveolar macrophages (NR8383). As in our model, the calculated IC 50 were respectively 16, 68, and more than 200 μg/mL for ZnO, ZnFe 2 O 4 , and Fe 2 O 3 ; global gene and protein expression profiles were only analyzed after exposure to ZnO and ZnFe 2 O 4 NPs. Using a rat genome microarray technology, we found that 985 and 1209 genes were significantly differentially expressed in NR8383 upon 4 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. It is noteworthy that metallothioneins were overexpressed genes following exposure to both NPs. Moreover, Ingenuity Pathway Analysis revealed that the top canonical pathway disturbed in NR8383 exposed to ZnO and ZnFe 2 O 4 NPs was eIF2 signaling involved in protein homeostasis. Quantitative mass spectrometry approach performed from both NR8383 cell extracts and culture supernatant indicated that 348 and 795 proteins were differentially expressed upon 24 h exposure to ¼ IC 50 of ZnO and ZnFe 2 O 4 NPs, respectively. Bioinformatics analysis revealed that the top canonical pathways disturbed in NR8383 were involved in protein homeostasis and cholesterol biosynthesis for both exposure conditions. While VEGF signaling was specific to ZnO exposure, iron homeostasis signaling pathway was specific to ZnFe 2 O 4 NPs. Overall, the study provides resource of transcriptional and proteomic markers of response to ZnO and ZnFe 2 O 4 NP-induced toxicity through combined transcriptomics, proteomics, and bioinformatics approaches.

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 96%

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

et al. 2019

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“…Thus, the attenuation of transmitted light comes from the combination of absorption and Rayleigh scattering. Other studies using the same Ag-NPs (NM300K) and ZnO-NPs (NM110) have reported smaller hydrodynamic sizes and higher stability [6,36,43,45]. As NPs' behavior depends on their surroundings [46], this highlights the importance of performing NP characterization with the same conditions as used in the experiments.…”

Section: Discussionmentioning

confidence: 91%

Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model

et al. 2020

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1) In compliance with the 3Rs policy to reduce, refine and replace animal experiments, the development of advanced in vitro models is needed for nanotoxicity assessment. Cells cultivated in 3D resemble organ structures better than 2D cultures. This study aims to compare cytotoxic and genotoxic responses induced by titanium dioxide (TiO 2 ), silver (Ag) and zinc oxide (ZnO) nanoparticles (NPs) in 2D monolayer and 3D spheroid cultures of HepG2 human liver cells. (2) NPs were characterized by electron microscopy, dynamic light scattering, laser Doppler anemometry, UV-vis spectroscopy and mass spectrometry. Cytotoxicity was investigated by the alamarBlue assay and confocal microscopy in HepG2 monolayer and spheroid cultures after 24 h of NP exposure. DNA damage (strand breaks and oxidized base lesions) was measured by the comet assay. (3) Ag-NPs were aggregated at 24 h, and a substantial part of the ZnO-NPs was dissolved in culture medium. Ag-NPs induced stronger cytotoxicity in 2D cultures (EC 50 3.8 µg/cm 2 ) than in 3D cultures (EC 50 > 30 µg/cm 2 ), and ZnO-NPs induced cytotoxicity to a similar extent in both models (EC 50 10.1-16.2 µg/cm 2 ). Agand ZnO-NPs showed a concentration-dependent genotoxic effect, but the effect was not statistically significant. TiO 2 -NPs showed no toxicity (EC 50 > 75 µg/cm 2 ). (4) This study shows that the HepG2 spheroid model is a promising advanced in vitro model for toxicity assessment of NPs.Nanomaterials 2020, 10, 545 2 of 21 and silver (Ag) is used as a disinfection agent in medical equipment and consumer products, on account of its antimicrobial activity [5]. Thus, humans are likely to be exposed to NPs, either intentionally or accidentally, during production and usage [6]. Transport of NPs across biological barriers has been observed by elemental analysis in both rodents and humans [7][8][9][10][11]. As an example, gold NPs have been reported to reach the systemic circulation in humans, after inhalation, and translocate to other organs [8,9].Several in vivo studies show that NPs accumulate in the liver, which is an important target organ for NPs and other xenobiotics due to its metabolic activity [12][13][14][15][16][17][18]. Induction of hepatotoxicity is one of the most common reasons for a medicine to be rejected or removed from the market [19,20]. Therefore, there is a need for sensitive hepatotoxicity screening methods for drug development and hazard assessment of chemicals or new materials, such as NPs. When considering the 3Rs-replacement, reduction and refinement-to minimize the use of animal experiments, hepatotoxicity should be assessed by reliable in vitro models. A great advantage of in vitro hepatocellular models for studying hepatotoxicity is the possibility of using human cells, either as primary cells or cell lines. The use of human hepatocyte cell lines, such as HepG2, C3A, Huh7 and HepaRG, has many advantages compared to primary cells. They are relatively easy to culture and have an unlimited life span, a relatively stable phenotype, high availability and ...

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“…Microarray were prepared as previously described [34]. Briefly, 100 ng of RNA from each sample was labeled with cyanine 3-CTP using Low Input Quick Amp Labeling assay ™ (Agilent Technologies; Waldbron; Germany) according to the manufacturer's protocol.…”

Section: Microarray Hybridizationmentioning

confidence: 99%

Genes expression profiling of alveolar macrophages exposed to non-functionalized, anionic and cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity

et al. 2020

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Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.© The Author(s) 2020. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article' s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article'

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Cytotoxicity and global transcriptional responses induced by zinc oxide nanoparticles NM 110 in PMA-differentiated THP-1 cells

Cited by 33 publications

References 32 publications

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Protein and lipid homeostasis altered in rat macrophages after exposure to metallic oxide nanoparticles

Hepato(Geno)Toxicity Assessment of Nanoparticles in a HepG2 Liver Spheroid Model

Genes expression profiling of alveolar macrophages exposed to non-functionalized, anionic and cationic multi-walled carbon nanotubes shows three different mechanisms of toxicity

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