A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

García-Salvador, Adrián; Katsumiti, Alberto; Rojas, Elena; Aristimuño, Carol; Betanzos, M.; Moro, Marta Martínez; Moya, Sergio; Goñi‐de‐Cerio, Felipe

doi:10.3390/nano11061577

Cited by 15 publications

(10 citation statements)

References 67 publications

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“…Therefore, to better understand the mechanisms of protection of CeO 2 -NPs observed in vivo, we performed experiments in an in vitro model of oxidative stress already used in our previously published paper [ 14 ]. Based on the results found in the literature, demonstrating the efficacy of CeO 2 -NPs at a concentration ranging from about 0.01 mM up to 0.5 mM in vitro, we used a concentration of 0.1 mM, a dose tenfold lower than that used in our in vivo experiment [ 30 , 31 , 32 ].…”

Section: Resultsmentioning

confidence: 99%

Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo

et al. 2022

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In this study, we investigated whether cerium oxide nanoparticles (CeO2-NPs), a promising antioxidant nanomaterial, may contrast retinal vascular alterations induced by oxidative damage in vitro and in vivo. For the in vivo experiments, the light damage (LD) animal model of Age-Related Macular Degeneration (AMD) was used and the CeO2-NPs were intravitreally injected. CeO2-NPs significantly decreased vascular endothelial growth factor (VEGF) protein levels, reduced neovascularization in the deep retinal plexus, and inhibited choroidal sprouting into the photoreceptor layer. The in vitro experiments were performed on human retinal pigment epithelial (ARPE-19) cells challenged with H2O2; we demonstrated that CeO2-NPs reverted H2O2-induced oxidative stress-dependent effects on this cell model. We further investigated the RPE–endothelial cells interaction under oxidative stress conditions in the presence or absence of CeO2-NPs through two experimental paradigms: (i) treatment of human umbilical vein endothelial cells (HUVECs) with conditioned media from ARPE-19 cells, and (ii) coculture of ARPE-19 and HUVECs. In both experimental conditions, CeO2-NPs were able to revert the detrimental effect of H2O2 on angiogenesis in vitro by realigning the level of tubule formation to that of the control. Altogether, our results indicate, for the first time, that CeO2-NPs can counteract retinal neovascularization and may be a new therapeutic strategy for the treatment of wet AMD.

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Section: Resultsmentioning

confidence: 99%

Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo

et al. 2022

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“…The imbalance between oxidants and antioxidants favors oxidants and may culminate in so-called “oxidative stress” ( Salvador et al, 2021 ). As a product of oxidative stress reaction, ROS produced by the interaction between nanomaterials and cells has been reported as one of the pivotal causes of cell damage.…”

Section: Resultsmentioning

confidence: 99%

Cytotoxicity Effect of Iron Oxide (Fe3O4)/Graphene Oxide (GO) Nanosheets in Cultured HBE Cells

Zhang

Yang

et al. 2022

Front. Chem.

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Iron oxide (Fe3O4), a classical magnetic material, has been widely utilized in the field of biological magnetic resonance imaging Graphene oxide (GO) has also been extensively applied as a drug carrier due to its high specific surface area and other properties. Recently, numerous studies have synthesized Fe3O4/GO nanomaterials for biological diagnosis and treatments, including photothermal therapy and magnetic thermal therapy. However, the biosafety of the synthesized Fe3O4/GO nanomaterials still needs to be further identified. Therefore, this research intended to ascertain the cytotoxicity of Fe3O4/GO after treatment with different conditions in HBE cells. The results indicated the time-dependent and concentration-dependent cytotoxicity of Fe3O4/GO. Meanwhile, exposure to Fe3O4/GO nanomaterials increased reactive oxygen species (ROS) levels, calcium ions levels, and oxidative stress in mitochondria produced by these nanomaterials activated Caspase-9 and Caspase-3, ultimately leading to cell apoptosis.

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“…22 However, provided the high frequency of applications in toxicological screening, this cell line represents a wellestablished model for human alveolar epithelium that can be used for cross-study comparisons. 7,23,24,25,26 In turn, the Calu-3 cells is a more obvious choice as a barrier model for the bronchial mucosa due to their excellent barrier maturation and tight junction formation properties. [27][28][29][30] Notably, Calu-3 cells have also been reported previously to form more physiological barrier models of the lung epithelium in comparison to other bronchial epithelial cell lines such as NHBE or NL-20.…”

Section: Discussion and Prospectsmentioning

confidence: 99%

“…5 In turn, inhalation of cerium oxide a prominent industrial process catalyst or other industrial by-products such as ultrafine carbon can result in a reduction of essential cellular and tissue physiological processes in the lung that can lead to strong inflammatory reactions. 6,7 Additionally, unintended inhalation of zinc oxide (ZnO) and titanium oxide (TiO2), which are widely applied NPs for UV protection in sunscreens, cosmetic powders, electronics, and paints are known to provoke dermal toxicity, dysregulation of immune cells and potential toxicological effects in lung tissue due to airborne consumption. 8,9 As an alternative to toxicological animal models, in vitro lung barrier systems exhibiting in vivo-like properties are often used to assess the health effects of airborne nanomaterials.…”

Section: Of 17mentioning

confidence: 99%

The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models

Stuetz¹,

Reihs²,

Neuhaus³

et al. 2023

Preprint

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As common industrial by-products, airborne engineered nanomaterials are considered important environmental toxicants to monitor due to their potential health risks to humans and animals. The main uptake routes of airborne nanoparticles are nasal and/or oral inhalation, which are known to enable the transfer of nanomaterials into the blood stream resulting in rapid distribution in the body. Consequently, mucosal barriers present in nose, buccal and lung have been identified and intensively studied as the key tissue barrier to nanoparticle translocation. Despite decades of research, surprisingly little is known about the differences among various mucosa tissue types to tolerate nanoparticle exposures. One limitation in comparing nanotoxicological data sets can be linked to a lack of harmonization and standardization of cell-based assays, where a) different cultivation conditions such as air-liquid interface or submerged cultures, b) varying barrier maturity and c) diverse media substitutes have been used. The current comparative nanotoxicological study therefore aims at analyzing the toxic effects of nanomaterials on four human mucosa barrier models including nasal (RPMI2650), buccal (TR146), alveolar (A549), and bronchial (Calu-3) mucosal cell lines to better understand the modulating effects of tissue maturity, cultivation conditions and tissue type using standard Transwell cultivations at liquid-liquid and air-liquid interfaces. Overall, cell size, confluency, tight junction localization, and cell viability as well as barrier formation using 50% and 100% confluency was monitored using trans-epithelial-electrical resistance (TEER) measurements and Presto Blue assays of immature (e.g. 5 days) and mature (e.g. 22 days) cultures in the presence and absence of corticosteroids such as hydrocortisone. Results of our study show that cellular responses to increasing nanoparticle exposures are highly cell type specific, where bronchial mucosal cell barriers models cultivated under ALI conditions showed less tolerance to acute ZnO nanoparticle exposures. Additionally, stronger toxicities are found using early mucosa barriers compared to later barrier models being maturated under air-liquid cultivation conditions.

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A Complete In Vitro Toxicological Assessment of the Biological Effects of Cerium Oxide Nanoparticles: From Acute Toxicity to Multi-Dose Subchronic Cytotoxicity Study

Cited by 15 publications

References 67 publications

Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo

Antioxidant Properties of Cerium Oxide Nanoparticles Prevent Retinal Neovascular Alterations In Vitro and In Vivo

Cytotoxicity Effect of Iron Oxide (Fe3O4)/Graphene Oxide (GO) Nanosheets in Cultured HBE Cells

The Cultivation Modality and Barrier Maturity Modulate the Toxicity of Industrial Zinc Oxide and Titanium Dioxide Nanoparticles on Nasal, Buccal, Bronchial, and Alveolar Mucosa Cell-Derived Barrier Models

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