Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: Acute toxicity, oxidative stress and oxidative damage

Xiong, Dao-wen; Fang, Tao; Li, Yu; Sima, Xiao-Feng; Zhu, Wentao

doi:10.1016/j.scitotenv.2011.01.015

Cited by 515 publications

(288 citation statements)

References 47 publications

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“…1b). This size effect difference is also reported by comparative cytotoxicity studies between fine and ultrafine materials 11 but not as the cause of ECL. We tested two other similarly sized NM, silicon dioxide and silver, and observed that these two other NM also caused ECL (Fig.…”

Section: Resultssupporting

confidence: 77%

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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The use of nanomaterials has raised safety concerns, as their small size facilitates accumulation in and interaction with biological tissues. Here we show that exposure of endothelial cells to TiO 2 nanomaterials causes endothelial cell leakiness. This effect is caused by the physical interaction between TiO 2 nanomaterials and endothelial cells' adherens junction protein VE-cadherin. As a result, VE-cadherin is phosphorylated at intracellular residues (Y658 and Y731), and the interaction between VE-cadherin and p120 as well as b-catenin is lost. The resulting signalling cascade promotes actin remodelling, as well as internalization and degradation of VE-cadherin. We show that injections of TiO 2 nanomaterials cause leakiness of subcutaneous blood vessels in mice and, in a melanoma-lung metastasis mouse model, increase the number of pulmonary metastases. Our findings uncover a novel non-receptor-mediated mechanism by which nanomaterials trigger intracellular signalling cascades via specific interaction with VE-cadherin, resulting in nanomaterial-induced endothelial cell leakiness.

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Section: Resultssupporting

confidence: 77%

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

et al. 2013

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“…Earlier studies supporting this hypothesis demonstrated significant decreases in various markers of toxicity (including survival, reproduction, and markers of oxidative stress) following exposure to micrometer-sized relative to nanosized (≤50 nm) TiO 2 for species such as zebrafish, 69 lugworms, 58 and nematodes. 70 However, the earthworm metabolic responses observed in the current study were very similar for both sizes of TiO 2 materials used (Figures 1and 2).…”

Section: ■ Discussionmentioning

confidence: 86%

Earthworm Sublethal Responses to Titanium Dioxide Nanomaterial in Soil Detected by ¹H NMR Metabolomics

Åslund

McShane

Simpson

et al. 2011

Environ. Sci. Technol.

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1H NMR-based metabolomics was used to examine the response of Eisenia fetida earthworms raised from juveniles for 20–23 weeks in soil spiked with either 20 or 200 mg/kg of a commercially available uncoated titanium dioxide (TiO2) nanomaterial (nominal diameter of 5 nm). To distinguish responses specific to particle size, soil treatments spiked with a micrometer-sized TiO2 material (nominal diameter, <45 μm) at the same concentrations (20 and 200 mg/kg) were also included in addition to an unspiked control soil. Multivariate statistical analysis of the 1H NMR spectra for aqueous extracts of E. fetida tissue suggested that earthworms exhibited significant changes in their metabolic profile following TiO2 exposure for both particle sizes. The observed earthworm metabolic changes appeared to be consistent with oxidative stress, a proposed mechanism of toxicity for nanosized TiO2. In contrast, a prior study had observed no impairment of E. fetida survival, reproduction, or growth following exposure to the same TiO2 spiked soils. This suggests that 1H NMR-based metabolomics provides a more sensitive measure of earthworm response to TiO2 materials in soil and that further targeted assays to detect specific cellular or molecular level damage to earthworms caused by chronic exposure to TiO2 are warranted.

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“…The antioxidant defense systems include a series of antioxidative enzymes and low-molecular non-enzymatic antioxidants, such as SOD activities, CAT activities and contents of MDA and GSH, which were all appropriate for monitoring oxidative stress status of fish after exposure to nano metal oxides (Hao et al 2009;Xiong et al 2011;Hao and Chen 2012;Lee et al 2012;Clemente et al 2013), in spite of the fact that some of the biomarker responses appear inconsistent because the mechanism is indirect as a consequence of the occlusion of tissue surfaces rather than more readily interpreted doseresponse relations. Indeed, the biomarker response varied in different organs and organs varied different sensitivity (detailed below), indicating possibly different toxicity mechanism.…”

Section: Discussionmentioning

confidence: 99%

“…Especially, gill is the primary organ contacting water born TiO 2 NPs, and gill could be suffering serious threat when TiO 2 NPs sticks to gill surface (Hao et al 2009;Xiong et al 2011;Hao and Chen 2012). Absolutely, gill is a more sensitive organ than others to monitor oxidative damage caused by TiO 2 NPs exposure, reflected by obvious change of SOD activities and content of MDA.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly, the 96 h exposed zebrafish eggs to up to 500 mg/L of TiO 2 NPs did not cause alterations in the survival and hatching rates, or malformations (Zhu et al 2008). However, water column species are the primary concern in the risk assessment strategy for contaminants (Handy et al 2012) and then sublethal effects have been observed, mainly related to oxidative stress and inflammation (Federici et al 2007;Hao et al 2009;Palaniappan and Pramod 2010;Xiong et al 2011;Lee et al 2012). It is likely that a subacute or chronic exposure may more acutely reveal the toxicity of TiO 2 NPs and be of more ecological importance in environmental risk evaluation.…”

Section: Introductionmentioning

confidence: 94%

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Effects of humic acid and ionic strength on TiO2 nanoparticles sublethal toxicity to zebrafish

Fang

Zhang

et al. 2015

Ecotoxicology

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The stability and bioavailability of titanium dioxide nanoparticles (TiO 2 NPs) suspension could be modified by the physicochemical properties of solution. In the present study, the effect of humic acid (HA) and ionic strength (by adding NaCl) on aggregation and sedimentation of TiO 2 NPs suspension were investigated. Accordingly, the sublethal toxicity of TiO 2 NPs suspensions with different HA and NaCl concentrations toward zebrafish (Danio rerio) was evaluated by monitoring the changes of superoxide dismutase, catalase, malonaldehyde and glutathione in gill, liver and intestine. The results showed that the aggregations formation and hydrodynamic diameter of TiO 2 NPs in suspensions are not essential characteristics to decide toxicity. The varied oxidative stress responses detected in gill, liver and intestine derived from different toxicity mechanisms of TiO 2 NPs. Nevertheless, the oxidative stress could be suppressed by the adding of HA and/or the increase of ionic strength, which can decrease the bioavailability of TiO 2 NPs in water. The study suggests that the environmental factors, such as HA and ionic strength, are important for the fate (aggregation and sedimentation) and toxicity of nanomaterials in aquatic environment.

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Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: Acute toxicity, oxidative stress and oxidative damage

Cited by 515 publications

References 47 publications

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Earthworm Sublethal Responses to Titanium Dioxide Nanomaterial in Soil Detected by ¹H NMR Metabolomics

Effects of humic acid and ionic strength on TiO2 nanoparticles sublethal toxicity to zebrafish

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Effects of nano-scale TiO2, ZnO and their bulk counterparts on zebrafish: Acute toxicity, oxidative stress and oxidative damage

Cited by 515 publications

References 47 publications

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Titanium dioxide nanomaterials cause endothelial cell leakiness by disrupting the homophilic interaction of VE–cadherin

Earthworm Sublethal Responses to Titanium Dioxide Nanomaterial in Soil Detected by 1H NMR Metabolomics

Effects of humic acid and ionic strength on TiO2 nanoparticles sublethal toxicity to zebrafish

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Earthworm Sublethal Responses to Titanium Dioxide Nanomaterial in Soil Detected by ¹H NMR Metabolomics