Metabolomics profiling to investigate nanomaterial toxicity <i>in vitro</i> and <i>in vivo</i>

Bannuscher, Anne; Hellack, Bryan; Bahl, Aileen; Laloy, Julie; Herman, Hildegard; Stan, Miruna Silvia; Dinischiotu, Anca; Giusti, Anna Maria; Krause, Benjamin; Tentschert, Jutta; Rosu, Marcel; Baltă, Cornel; Wiemann, Martin; Luch, Andreas; Haase, Andrea

doi:10.1080/17435390.2020.1764123

Cited by 31 publications

(32 citation statements)

References 82 publications

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“…After STIS and instillations, the frozen lungs were homogenized as described before [80], and proteins as well as metabolites were extracted according to the in vitro studies.…”

Section: Sample Preparation For Omics Studiesmentioning

confidence: 99%

“…The here presented metabolomics data were published before [80] but re-evaluated in analogy to the proteomics data. In brief, the AbsoluteIDQ p180 Kit (Biocrates, Austria) was used as described previously [11,12,80,81], and samples were analyzed with an API 5500 triple quadrupole mass spectrometer (ABSciex, Germany), coupled to an Agilent 1260 In nity HPLC system (Agilent, USA). Analyst® software and MetIDQ were used for data analysis.…”

Section: Targeted Metabolomics and Untargeted Proteomicsmentioning

confidence: 99%

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Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

Karkossa

Bannuscher

Hellack³

et al. 2020

Preprint

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Background The immense variety and constant development of nanomaterials (NMs) raise the demand for a facilitated risk assessment, for which knowledge on NMs mode of actions (MoAs) is required. For this purpose, a comprehensive data basis is of paramountcy that can be obtained using omics. Furthermore, the establishment of suitable in vitro test systems is indispensable to follow the 3R concept and to master the high number of NMs. In the present study, we aimed at comparing NM effects in vitro and in vivo using a multi-omics approach. We applied an integrated data evaluation strategy based on proteomics and metabolomics to four silica NMs and one titanium dioxide-based NM. For in vitro investigations, alveolar epithelial cells and alveolar macrophages were treated with different doses of NMs, and the results were compared to effects on rat lungs after short-term inhalations and instillations at varying doses with and without a recovery period.Results Since the production of reactive oxygen species (ROS) is described to be a critical biological effect of NMs, and enrichment analyses confirmed oxidative stress as a significant effect upon NM treatment in vitro in the present study, we focused on different levels of oxidative stress. Thus, we found opposite changes for proteins and metabolites that are related to the production of reduced glutathione in alveolar epithelial cells and alveolar macrophages, illustrating that NMs MoAs depend on the used model system. Interestingly, in vivo, pathways related to inflammation were affected to a greater extent than oxidative stress responses. Hence, the assignment of the observed effects to the levels of oxidative stress was different in vitro and in vivo as well. However, the overall classification of “active” and “passive” NMs was consistent in vitro and in vivo.Conclusions The consistent classification indicates both tested cell lines to be suitable for NM toxicity assessment even though the induced levels of oxidative stress strongly depend on the used model systems. Thus, the here presented results highlight that model systems need to be carefully revised to decipher the extent to which they can replace in vivo testing.

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“…After STIS and instillations, the frozen lungs were homogenized as described before [80], and proteins as well as metabolites were extracted according to the in vitro studies.…”

Section: Sample Preparation For Omics Studiesmentioning

confidence: 99%

Section: Targeted Metabolomics and Untargeted Proteomicsmentioning

confidence: 99%

Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

Karkossa

Bannuscher

Hellack³

et al. 2020

Preprint

Self Cite

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“…1A. The study has been conducted under the framework of ERA-NET SIINN NanoToxClass project, as previously described [47]. Brie y, aSiO 2 NMs (SiO 2 _15_Unmod, SiO 2 _15_Amino, SiO 2 _40 and SiO 2 _7) were dispersed by indirect probe sonication using a Bandelin Cup Horn (Bandelin, Germany) according to the internal Standard Operating Procedure (SOP) of NanoToxClass consortium.…”

Section: Intratracheal Instillation Studymentioning

confidence: 99%

“…STIS has been also conducted under the framework of NanoToxClass project, as previously described [47]. The study was approved by the Committee on the Ethics of Animal Experiments of the University of Namur, Belgium) under the agreement UN 18306 DO.…”

Section: Short-term Inhalation Study (Stis)mentioning

confidence: 99%

“…The aerosols were generated by an RBG-1000 (Palas GmbH, Germany) generator and analysed in realtime by ELPI analyzer (Dekati Ltd., Finland), capable of particle measurement between 7 nm and 10 µm (Lozano et al, 2018). SiO 2_ 7 has been selected for this study based on OMICs data analyses that revealed more pronounced effects at pulmonary level in the rats exposed to this variant [47]. Selection of realistic tested doses was based on the calculation of the deposited doses used in the in vivo instillation study using the Multiple-Path Particle Deposition model (MPPD, version 3.04, ARA) to assure prevention of overload effects.…”

Section: Short-term Inhalation Study (Stis)mentioning

confidence: 99%

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Genotoxicity and Gene Expression in the Rat Lung Tissue Following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NMs)

Brandão

Costa

Bessa

et al. 2020

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Background: Synthetic amorphous silica (SAS) has been widely used in several industrial and consumer applications for decades and considered safe for humans. However, several reports on the in vitro and in vivo toxicity of amorphous silica nanomaterials (aSiO2 NMs) have been questioning its safety at the nanoscale. In the present study, we investigated the influence of the physicochemical properties (size and surface chemistry) on in vivo pulmonary toxicity using four variants of aSiO2 NMs (SiO2_15_Unmod, SiO2_15_Amino, SiO2_7 and SiO2_40). We focused on alterations in lung DNA and protein integrity, and gene expression following intratracheal instillation in rats. Additionally, a short-term inhalation study (STIS) was carried out for SiO2_7, using TiO2_NM105 as a benchmark NM.Results: Overall, single intratracheal instillation of all tested NMs did not cause a significant increase of DNA strand breaks in the rat lung. However, a significant but slight increase of oxidative DNA damage in rats exposed to the highest instilled dose (0.36 mg/rat) of SiO2_15_ Amino was observed at 21 days post-exposure. In turn, exposure to SiO2_7 or SiO2_40 markedly increased oxidative DNA lesions in the rat lung cells in every tested dose at 3 days post-exposure, even though in a dose-independent manner. Nevertheless, this damage seems to be repaired since no changes compared to controls were observed in the recovery groups. In STIS, a significant increase of DNA strand breaks in the lung cells of rats exposed to 0.5 mg/m3 of SiO2_7 or to 50 mg/m3 of TiO2_NM105 was observed at both assessed time-points. The gene expression changes detected suggest that oxidative stress and/or inflammation pathways are likely implicated in the induction of (oxidative) DNA damage.Conclusions: Overall, all tested aSiO2 NMs were not associated with marked in vivo toxicity following instillation or STIS. Under our experimental conditions, pyrogenic aSiO2 NMs (SiO2_7 and SiO2_40) showed a higher genotoxic potential compared to colloidal aSiO2 (SiO2_15_Unmod and SiO2_15_Amino). Overall, genotoxicity findings for SiO2_7 from instillation and STIS are concordant, however changes in STIS animals were more permanent/difficult to revert.

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Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

Cao

2021

J of Applied Toxicology

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The development of nanotechnology leads to the exposure of human beings to nanomaterials (NMs), and there is a health concern about the adverse vascular effects of NMs. Current data from epidemiology, controlled human exposure, and animal studies suggested that exposure to NMs could induce cardiopulmonary effects. In support of in vivo findings, in vitro studies showed that direct contact of vascular cells with NMs could induce endothelial cell (EC) activation and promote macrophage foam cell formation, although only limited studies showed that NMs could damage vascular smooth muscle cells and promote their phenotypic switch. It has been proposed that NMs induced adverse vascular effects via different mechanisms, but it is still necessary to understand the upstream events. Kruppel‐like factors (KLFs) are a set of C2H2 zinc finger transcription factors (TFs) that can regulate various aspects of vascular biology, but currently, the roles of KLF2 in mediating the adverse vascular effects of NMs have gained little attention by toxicologists. This review summarized current knowledge about the adverse vascular effects of NMs and proposed the potential roles of KLFs in mediating these effects based on available data from toxicological studies as well as the current understanding about KLFs in vascular biology. Finally, the challenges in investigating the role of KLFs in vascular toxicology were also summarized. Considering the important roles of KLFs in vascular biology, further studies are needed to understand the influence of NMs on KLFs and the downstream events.

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Metabolomics profiling to investigate nanomaterial toxicity in vitro and in vivo

Cited by 31 publications

References 82 publications

Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

Nanomaterials induce different levels of oxidative stress, depending on the used model system: Comparison of in vitro and in vivo effects

Genotoxicity and Gene Expression in the Rat Lung Tissue Following Instillation and Inhalation of Different Variants of Amorphous Silica Nanomaterials (aSiO2 NMs)

Potential roles of Kruppel‐like factors in mediating adverse vascular effects of nanomaterials: A review

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