Short- and long-term gene expression profiles induced by inhaled TiO2 nanostructured aerosol in rat lung

Chézeau, Laëtitia; Sébillaud, Sylvie; Safar, Ramia; Seidel, Carole; Dembélé, Doulaye; Lorcin, Mylène; Langlais, Cristina; Grossmann, Stéphane; Nunge, Hervé; Michaux, Sylvie; Dubois-Pot-Schneider, Hélène; Rihn, Bertrand; Joubert, O.; Binet, Stéphane; Cosnier, Frédéric; Gaté, Laurent

doi:10.1016/j.taap.2018.07.013

Cited by 19 publications

(32 citation statements)

References 63 publications

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“…The presence of a strong pulmonary inflammation at the end of the exposure, agrees with these data. Finally, the presence of macrophages loaded with TiO 2 NP in the alveoli and the lymph nodes associated with the lungs [22], suggests a conservation of the mechanisms of particle elimination, by the mucociliary escalator or by translocation from the alveolar region to the lymph nodes. These results demonstrate the key role of alveolar macrophages in the pulmonary response to nanoparticle inhalation and justify the comparison of in vivo response with that of cultured rat alveolar macrophages.…”

Section: Number Of Degs In Each Exposure Methodsmentioning

confidence: 96%

“…No common BP for ALI and in vitro submerged conditions or for the three conditions were evidenced. More connections between the DEGs were found in vitro (22) and in vivo (16) than in ALI conditions (6), and for all the groups, the software indicated that the genes are at least partially biologically connected as a group ( Figure S1).…”

Section: Transcriptomic Analysis Of Dysregulated Genes Following In Vmentioning

confidence: 99%

“…The in vivo exposure was made at the National Institute for Research and Safety (INRS) and described previously [22]. Briefly, thirteen-week-old male Fisher F344 rats (Charles River Laboratories, France) were housed in standard environmental conditions (relative humidity: 55 ± 10 %; temperature: 22 ± 2 • C and 12/ 12 h light/dark cycle).…”

Section: In Vivo Exposurementioning

confidence: 99%

“…Gene expression was analyzed by transcriptomic analysis on the entire pulmonary accessory lobe. We reanalyzed the transcriptomic results obtained in vivo (GEO Accession: GSE99997) [22] in order to compare them with the results obtained in vitro and in ALI conditions.…”

Section: In Vivo Exposurementioning

confidence: 99%

“…NR8383 rat lung macrophages are relevant due to their immune functions and it is a validated model for nanotoxicological studies [20,21]. In the present work, we used this cell line with two types of exposure (submerged and ALI) compared to an in vivo rat exposure [22] to validate alternative models for nanotoxicological studies.…”

Section: Introductionmentioning

confidence: 99%

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Toxicity of TiO2 Nanoparticles: Validation of Alternative Models

Leroux

Doumandji

Chézeau

et al. 2020

IJMS

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There are many studies concerning titanium dioxide (TiO2) nanoparticles (NP) toxicity. Nevertheless, there are few publications comparing in vitro and in vivo exposure, and even less comparing air–liquid interface exposure (ALI) with other in vitro and in vivo exposures. The identification and validation of common markers under different exposure conditions are relevant for the development of smart and quick nanotoxicity tests. In this work, cell viability was assessed in vitro by WST-1 and LDH assays after the exposure of NR8383 cells to TiO2 NP sample. To evaluate in vitro gene expression profile, NR8383 cells were exposed to TiO2 NP during 4 h at 3 cm2 of TiO2 NP/cm2 of cells or 19 μg/mL, in two settings—submerged cultures and ALI. For the in vivo study, Fischer 344 rats were exposed by inhalation to a nanostructured aerosol at a concentration of 10 mg/m3, 6 h/day, 5 days/week for 4 weeks. This was followed immediately by gene expression analysis. The results showed a low cytotoxic potential of TiO2 NP on NR8383 cells. Despite the absence of toxicity at the doses studied, the different exposures to TiO2 NP induce 18 common differentially expressed genes (DEG) which are involved in mitosis regulation, cell proliferation and apoptosis and inflammation transport of membrane proteins. Among these genes, we noticed the upregulation of Ccl4, Osm, Ccl7 and Bcl3 genes which could be suggested as early response biomarkers after exposure to TiO2 NP. On the other hand, the comparison of the three models helped us to validate the alternative ones, namely submerged and ALI approaches.

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Section: Number Of Degs In Each Exposure Methodsmentioning

confidence: 96%

Section: Transcriptomic Analysis Of Dysregulated Genes Following In Vmentioning

confidence: 99%

Section: In Vivo Exposurementioning

confidence: 99%

Section: In Vivo Exposurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Toxicity of TiO2 Nanoparticles: Validation of Alternative Models

Leroux

Doumandji

Chézeau

et al. 2020

IJMS

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Research progress on toxicity, function, and mechanism of metal oxide nanoparticles on vascular endothelial cells

Wang

Tang

2020

J of Applied Toxicology

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Metal oxide nanoparticles present stable and unique performance that makes them suitable for various biomedical applications. There are four common exposure ways that nanoparticles enter our body: injection, inhalation, skin penetration, and ingestion. Among them, injection, ingestion, and skin routes may become significant ways for nano‐scale treatment and cosmetics, and inhalation is the essential way for occupational exposure. All those nanoparticles could pass through the exposure routes and enter the circulation, which could cause damage on the cardiovascular system. So it is necessary to evaluate the toxicity of metal oxide nanoparticles and to explore the mechanism. This review chose four commonly used nanometal oxides to discuss about the toxicity they produced, the function they affected, and the mechanisms on cardiovascular endothelial cells. First, we discussed the toxicity they caused. These nanoparticles are less toxic when applied in low doses, but owing to the small particle size and large specific surface area, acute exposure or the metal ions released by nanoparticles will lead to phenotypic changes of endothelial cells, oxidative stress, and apoptosis. An endothelial cell is an essential part of blood vessels and could act as a barrier, maintain vascular tension, and keep the balance between coagulation and anticoagulation. Once vascular endothelium is injured or exposed to vascular risk factors, it would cause endothelial activation, endothelial dysfunction, and nitric oxide (NO) synthase (NOS) dysfunction, which are closely related to the cardiovascular disease. Finally, we talked about the mechanisms by four levels, and we especially mentioned inflammation, the production of reactive oxygen species, and NO.

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Quantifying Titanium Exposure in Lung Tissues: A Novel Laser‐Induced Breakdown Spectroscopy Elemental Imaging‐Based Analytical Framework for Biomedical Applications

Gardette,

Sancey,

Leprince

et al. 2024

Small Science

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Occupational and environmental exposures, particularly those related to urban and suburban atmospheres, are increasingly linked to a range of pulmonary diseases. While diagnostic methods for these diseases are well established, analytical tools for assessing elemental contamination in lung tissue remain underutilized. This study introduces a novel framework based on laser‐induced breakdown spectroscopy (LIBS) for the in situ quantification of elemental titanium (Ti) in lung tissues from both animal models and human specimens. Rigorous validation is conducted using animal models exposed to TiO2 P25 nanoparticles and a comparative analysis with inductively coupled plasma mass spectrometry. The novel quantitative metric demonstrates robust correlation with elemental concentrations, expanding LIBS utility to volumetric organ analysis. This validated methodology is subsequently applied to human lung specimens preserved in paraffin. The research holds significant promise as a diagnostic tool for assessing exposure levels to environmental or occupational hazards, thereby offering valuable contributions to the fields of toxicology and respiratory medicine.

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Short- and long-term gene expression profiles induced by inhaled TiO2 nanostructured aerosol in rat lung

Cited by 19 publications

References 63 publications

Toxicity of TiO2 Nanoparticles: Validation of Alternative Models

Toxicity of TiO2 Nanoparticles: Validation of Alternative Models

Research progress on toxicity, function, and mechanism of metal oxide nanoparticles on vascular endothelial cells

Quantifying Titanium Exposure in Lung Tissues: A Novel Laser‐Induced Breakdown Spectroscopy Elemental Imaging‐Based Analytical Framework for Biomedical Applications

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