<i>In situ</i>quantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Simón, Marina; Saez, Gladys; Muggiolu, Giovanna; Lavenas, Magali; Trequesser, Quentin Le; Michelet, Claire; Devès, Guillaume; Barberet, Philippe; Chevet, Éric; Dupuy, Denis; Delville, Marie‐Hélène; Seznec, Hervé

doi:10.1080/17435390.2017.1278803

Cited by 37 publications

(31 citation statements)

References 68 publications

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“…Furthermore, we showed that long-term treatment of mice by chromium disilicide nanoparticles only strongly suppressed the expression of IGFBP2 and PECAM1 genes in the liver. It is possible that our results with SNARK/NUAK2, IGFBP2, and PECAM1 genes expression also refl ect the genotoxic eff ect of titanium nitride and chromium disilicide nanoparticles and are mostly consistent with previously reported data (Ze et al 2014;Alarifi et al 2016;Yang et al 2016;Simon et al 2017), which clearly demonstrated that titanium dioxide nanoparticles are internalized into the cells, aff ect the expression of numerous genes and disrupt cell metabolic functions, resulting in dysregulation of cell proliferation and apoptosis.…”

Section: Igfbp3 Igfbp4supporting

confidence: 81%

“…For titanium dioxide nanoparticles, which are widely used in the number of applications, including cosmetic creams, toothpastes, and component of surgical implants, it has been shown that long-term exposure to these nanoparticles led to accumulation of these nanoparticles in brain, over-proliferation of glial cells and signifi cant changes in brain gene expressions as well as to neurogenic disease states in mice (Ze et al 2014;Rollerova et al 2015). Moreover, titanium dioxide nanoparticles synthesized as nanoneedles, titanate scrolled nanosheets, and gel-sol-based isotropic nanoparticle aff ect intracellular calcium homeostasis, thereby leading to endoplasmic reticulum stressdependent toxicity (Simon et al 2017). However, the genotoxicity of titanium nitride nanoparticles, which have favorable properties and are used for coronary stents, syringe needles, and the coating of orthopedic implant as well as in dental medicine for improving long-term implants (van Hove et al 2015;Chu et al 2016;Karjalainen and Nammas 2016;Ritz et al 2016), has not been studied yet.…”

Section: Discussionmentioning

confidence: 99%

“…Th ese nanoparticles, which were synthesized as nanoneedles, titanate scrolled nanosheets, and gelsol-based isotropic nanoparticle, were internalized at various degrees and their toxicity depended on both the titanium content and nanoparticles shape. Diverse titanium dioxide nanoparticles aff ect intracellular calcium homeostasis, thereby leading to endoplasmic reticulum stress-dependent toxicity (Simon et al 2017). Th ere are data that chromium disilicide nanowires are attractive choices for future applications in magnetic storage, photovoltaic, and fi eld emitters (Hsu et al 2015), but the toxicity of chromium disilicide nanoparticles has not been studied yet.…”

mentioning

confidence: 99%

“…Furthermore, Yang et al (2016) have shown that oral administration of titanium dioxide nanoparticles disrupts hepatic metabolic functions in a mouse model. Recently, it has been shown that titanium dioxide nanoparticles have possible impact on health due to their specifi c properties supported by their size and geometry (Simon et al 2017). Th ese nanoparticles, which were synthesized as nanoneedles, titanate scrolled nanosheets, and gelsol-based isotropic nanoparticle, were internalized at various degrees and their toxicity depended on both the titanium content and nanoparticles shape.…”

mentioning

confidence: 99%

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Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

Minchenko

Tsymbal

Yavorovsky

et al. 2017

Endocrine Regulations

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Objective. Th e aim of the present study was to examine the eff ect of chromium disilicide and titanium nitride nanoparticles on the expression level of genes encoding important regulatory factors (IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK/NUAK2, CD36, and PECAM1/CD31) in mouse liver for evaluation of possible toxic eff ects of these nanoparticles.Methods. Male mice received 20 mg chromium disilicide nanoparticles (45 nm) and titanium nitride nanoparticles (20 nm) with food every working day for 2 months. Th e expression of IGFBP1, IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver was studied by quantitative polymerase chain reaction.Results. Treatment of mice with chromium disilicide nanoparticles led to down-regulation of the expression of IGFBP2, IGFBP5, PECAM1, and SNARK genes in the liver in comparison with control mice, with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3 and CD36 genes was increased in mouse liver upon treatment with chromium disilicide nanoparticles. We have also shown that treatment with titanium nitride nanoparticles resulted in down-regulation of the expression of IGFBP2 and SNARK genes in the liver with more prominent changes for SNARK gene. At the same time, the expression of IGFBP3, IGFBP4, and CD36 genes was increased in the liver of mice treated with titanium nitride nanoparticles. Furthermore, the effect of chromium disilicide nanoparticles on IGFBP2 and CD36 genes expression was signifi cantly stronger as compared to titanium nitride nanoparticles.Conclusions. Th e results of this study demonstrate that chromium disilicide and titanium nitride nanoparticles have variable eff ects on the expression of IGFBP2, IGFBP3, IGFBP4, IGFBP5, SNARK, CD36, and PECAM1 genes in mouse liver, which may refl ect the genotoxic activities of the studied nanoparticles. A rapid development of nanoscience and nanotechnologies has given a rise to the wide range of applications of man-made nanomaterials in specifi c biomedical fi elds for treatment, diagnosing, controlling, and repairing of biological systems at the molecular level. Titanium nitride nanoparticles have favorable properties and are used for the coating of orthopedic implants, coronary stents, and syringe needles as well as for improving long-term implants in the dental medicine. However, very little is known Unauthenticated Download Date | 5/12/18 12:12 PM

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Section: Igfbp3 Igfbp4supporting

confidence: 81%

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

Minchenko

Tsymbal

Yavorovsky

et al. 2017

Endocrine Regulations

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“…Both a‐ZnO MS and c‐ZnO MS significantly promoted the expression of ER stress‐apoptosis genes. This could be because they contained sheet‐like structures, and a recent study already showed that TiO 2 NPs with nanosheet structures induced a pronounced ER stress in vitro (Simon et al, ). Surprisingly, ZnO Mini‐NRs, which were as cytotoxic as ZnO NRs, did not significantly influence the expression of ER stress‐apoptosis genes (Figures and ).…”

Section: Discussionmentioning

confidence: 99%

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles

Yan

Jiang

Liu

et al. 2018

J of Applied Toxicology

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Understanding the possible role of physicochemical properties in determining the toxicity of ZnO nanomaterials (NMs) is crucial for the safe use of ZnO-based materials. In this study, we synthesized four types of ZnO NMs, and characterized them as ZnO nanorods (NRs; length 400-500 nm, diameter 150-200 nm), ZnO Mini-NRs (length 50-100 nm, diameter 15-20 nm), amorphous ZnO microspheres (a-ZnO MS) and crystalline ZnO MS (c-ZnO MS; the a/c-ZnO MS are nanoflowers with an extensive growth of sheet-like structures). ZnO NMs and ZnO Mini-NRs were significantly more cytotoxic than a/c-ZnO MS, and this trend was similar in both HepG2 cells and human umbilical vein endothelial cells. Intracellular reactive oxygen species was only modestly induced by c-ZnO MS, whereas intracellular Zn ions were dose-dependently increased in HepG2 cells by the exposure of all types of ZnO NMs. The expression of endoplasmic reticulum stress marker DDIT3 was induced following an order of ZnO NRs > a-ZnO MS > c-ZnO MS > ZnO Mini-NRs, and the apoptosis gene CASP12 was induced following an order of a-ZnO MS > ZnO NRs > c-ZnO MS > ZnO Mini-NRs. Combined, these results suggested that ZnO NM-induced cytotoxicity and expression of endoplasmic reticulum stress-apoptosis genes could be influenced by the size and shape of ZnO NMs.

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Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles

Liu¹,

Tang

2019

J of Applied Toxicology

108

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Owing to the increasing application of engineered nanoparticles (NPs), besides the workplace, human beings are also exposed to NPs from nanoproducts through the skin, respiratory tract, digestive tract and vein injection. This review states pathways of cellular uptake, subcellular distribution and excretion of NPs. The uptake pathways commonly include phagocytosis, micropinocytosis, clathrin‐ and caveolae‐mediated endocytosis, scavenger receptor‐related pathway, clathrin‐ or caveolae‐independent pathway, and direct penetration or insertion. Then the ability of NPs to decrease cell viability and metabolic activity, change cell morphology, and destroy cell membrane, cytoskeleton and cell function was presented. In addition, the lowest dose decreasing cell metabolic viability compared with the control or IC50 of silver, titanium dioxide, zinc oxide, carbon black, carbon nanotubes, silica, silicon NPs and cadmium telluride quantum dots to some cell lines was gathered. Next, this review attempts to increase our understanding of NP‐caused adverse effects on organelles, which have implications in mitochondrial dysfunction, endoplasmic reticulum stress and lysosomal rupture. In particular, the disturbance of mitochondrial biogenesis and mitochondrial dynamic fusion‐fission, mitophagy and cytochrome c‐dependent apoptosis are involved. In addition, prolonged endoplasmic reticulum stress will result in apoptosis. Rupture of the lysosomal membrane was associated with inflammation, and both induction of autophagy and blockade of autophagic flow can result in cytotoxicity. Finally, the network mechanism of the combined action of multiple organelle dysfunction, apoptosis, autophagy and oxidative stress was discussed.

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In situquantification of diverse titanium dioxide nanoparticles unveils selective endoplasmic reticulum stress-dependent toxicity

Cited by 37 publications

References 68 publications

Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

Expression of genes encoding IGFBPs, SNARK, CD36, and PECAM1 in the liver of mice treated with chromium disilicide and titanium nitride nanoparticles

The toxicity of ZnO nanomaterials to HepG2 cells: the influence of size and shape of particles

Toxic effects and involved molecular pathways of nanoparticles on cells and subcellular organelles

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