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1.
Artigo em Chinês | MEDLINE | ID: mdl-33781031

RESUMO

Objective: To explore the chronic toxicity and its potential mechanism of multi-walled carbon nanotube (MWCNT) in human pleural mesothelial cells. Methods: A sustainable exposure of MeT-5A cells to MWCNT at 10 µg/cm(2) for one year was conducted in 2016. During the exposure, the cell images and cell proliferation was recorded every 4 weeks. The cell apoptosis, cell cycle, cell migration and cell invasion were compared between the control cells and the cells after MWCNT exposure. Finally, the gene expression was screened with Affymetrix clariom D assay, and some of the significantly differential expressed genes was verified by RT-PCR. Results: Compared with the control group, the proliferation ability of the cells in the 1-year exposed group was significantly increased, and the rate of proliferation was about 2-3 times as that in the Control Group (F=481.32, P<0.05) . MeT-5A cells all showed cell cycle arrest effect, which showed the increase of G1 phase and the decrease of s phase and G2 phase (F=14.94, P<0.05) . The apoptosis rate of cells in the treated group was significantly higher than that in the control group after 6 months (F=15.12, P<0.05) , but the early apoptosis rate and the total apoptosis rate of cells in the treated group were not significantly different from those in the control group after 1 year (F=3.97, P<0.05) . The cell migration and invasion were both promoted by MWCNT. Furthermore, the differentially expressed genes was screened, to find 2, 878 genes with more than 2 folds changes. To further verified, RT-PCR was conducted with PIK3R3、WNT2B、VANGL2、ANXA1, and their expression changes were consistent with above. Conclusion: MWCNT might have a carcinogenic potential to MeT-5A cells after the long term exposure.


Assuntos
Nanotubos de Carbono , Apoptose , Carcinógenos , Ciclo Celular , Proliferação de Células , Humanos , Nanotubos de Carbono/toxicidade , Fosfatidilinositol 3-Quinases
2.
Chemosphere ; 271: 129775, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33736227

RESUMO

In the marine environment, organisms are exposed to a high and increasing number of different contaminants that can interact among them. In addition, abiotic factors can change the dynamics between contaminants and organisms, thus increasing or even decreasing the toxic effect of a particular compound. In this study, the effects of caffeine (CAF) and functionalized multi-walled carbon nanotubes (f-MWCNTs) induced in the clam Ruditapes philippinarum were evaluated, acting alone and in combination (MIX), under two temperature levels (18 and 21 °C). To assess the impact of such compounds, their interaction and the possible influence of temperature, biochemical and histopathological markers were investigated. The effects of f-MWCNTs and caffeine appear to be clearly negative at the control temperature, with lower protein content in contaminated clams and a significant decrease in their metabolism when both pollutants were acting in combination. Also, at control temperature, clams exposed to pollutants showed increased antioxidant capacity, especially when caffeine was acting alone, although cellular damages were still observed at CAF and f-MWCNTs treatments. Increased biotransformation capacity at 18 °C and MIX treatment may explain lower caffeine concentration observed. At increased temperature differences among treatments were not so evident as at 18 °C, with a similar biological pattern among contaminated and control clams. Higher caffeine accumulation at MIX treatment under warming conditions may result from clams' inefficient biotransformation capacity when exposed to increased temperatures.


Assuntos
Bivalves , Nanotubos de Carbono , Poluentes Químicos da Água , Animais , Cafeína/toxicidade , Nanotubos de Carbono/toxicidade , Estresse Oxidativo , Temperatura , Poluentes Químicos da Água/toxicidade
3.
Sci Total Environ ; 769: 145156, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33477045

RESUMO

Agricultural chemicals have the potential to become pollutants that adversely affect plant growth. Interactions between these compounds are likely, but potential synergies are under-researched. Multiwall carbon nanotubes are increasingly finding novel uses in agriculture, as delivery mechanisms and as slow-release fertilizers. There is potential for nanotubes to interact with other agricultural chemicals in unpredictable ways. To investigate this possibility, we examined interactions with glyphosate, a widely used herbicide that is also attracting increasing concern over its potential for non-target effects. Here we examined potential synergistic effects on hydroponically grown Arabidopsis thaliana. Single treatments did not affect plant growth significantly, or did only mildly. However, combined treatment significantly affected both plant root and shoot growth. High-level content of malondialdehyde and up-regulated of metabolic antioxidant molecules in plant indicated that combined group caused the strong oxidative damage, while the decreased of antioxidant enzyme activities indicated an imbalance between reactive oxygen species (ROS)and the antioxidant defense system due to the continuously generated ROS. Besides, several intermediate metabolites of unsaturated fatty acids synthesis pathways were up-regulated in combined treatment, which clarified that combined group changed membrane components. The increase of intermediate metabolites in combined group also reflected more energy consumption in the repairment of the disrupt of combined treatment. The synergistic effect observed was attributed to the accumulation of glyphosate resulting from permeability and transportability of the carbon nanotubes. Overall, the risk of nanotube-herbicide interaction suggests a caution use of nanotubes in agricultural applications.


Assuntos
Arabidopsis , Nanotubos de Carbono , Glicina/análogos & derivados , Glicina/toxicidade , Nanotubos de Carbono/toxicidade , Estresse Oxidativo
4.
Nanotoxicology ; 15(2): 238-256, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33332178

RESUMO

Inhalation of multi-walled carbon nanotubes (MWCNTs) induces lung inflammation. Depending on industrial applications, CNTs with different physicochemical characteristics are produced and workers can potentially be exposed. This raises concerns about the long-term health effects of these nanomaterials. Because of the wide variety of MWCNTs, it is essential to study the toxicological effects of CNTs of various shapes and to better understand the impact physical and chemical properties have on their toxicity. In this study, rats were exposed by nose-only to two pristine MWCNTs with different morphologies: the long and thick NM-401 or the short and thin NM-403. After four weeks of inhalation, animals were euthanized at four different times during the recovery period: three days (short-term), 30 and 90 days (intermediate-term) and 180 days (long-term). Analyses of the transcriptome in the whole lung and the proteome in the bronchoalveolar lavage fluid of exposed animals were performed to understand the MWCNT underlying mechanisms of toxicity. Following inhalation of NM-401, we observed a dose-dependent increase in the number of differentially expressed genes and proteins, whereas there is no clear difference between the two concentrations of NM-403. After NM-403 inhalation, the number of differentially expressed genes and proteins varied less between the four post-exposure times compared to NM-401, which supports the postulation of a persistent effect of this type of CNT. Our toxicogenomics approaches give insights into the different toxicological profile following MWCNT exposure.


Assuntos
Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pneumonia/induzido quimicamente , Proteoma/metabolismo , Transcriptoma/efeitos dos fármacos , Administração por Inalação , Animais , Líquido da Lavagem Broncoalveolar/química , Feminino , Nanotubos de Carbono/química , Pneumonia/metabolismo , Ratos , Ratos Sprague-Dawley , Propriedades de Superfície , Toxicogenética
5.
Chemosphere ; 262: 128053, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33182130

RESUMO

Nowadays, more and more attention is focused on the environmental harm brought by the wide production and use of carbon nanotubes. In this study, the metabolic function of sediment microbial community was investigated after unfunctionalized or functionalized multi-walled carbon nanotubes (MWCNTs) were incorporated. The surface functional groups on the studied functionalized MWCNTs in this work were hydroxyl, carboxyl, and amino, respectively. The metabolic functional diversity was determined by Biolog EcoPlates after one-month exposure to MWCNTs. Incorporating 0.5 wt% amino functionalized MWCNTs significantly decreased the microbial activity and diversity, and all types of MWCNTs caused great inhibition on the microbial metabolism at the dosage of 2.0 wt%. The sediment microbes preferred polymers and amino acids. Principal component and similarity analysis indicated that the microbial carbon metabolism was more affected by the MWCNT dosage compared with the functionalization, and 2.0 wt% amino functionalized MWCNTs made the greatest difference in metabolic function of sediment microbial community. These consequences may help to assess the environmental risks of MWCNTs from the aspect of ecological relevance of sediment microbial community.


Assuntos
Sedimentos Geológicos/microbiologia , Microbiota/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Rios/microbiologia , Poluentes Químicos da Água/toxicidade , Sedimentos Geológicos/química , Modelos Teóricos , Nanotubos de Carbono/química , Rios/química , Propriedades de Superfície , Poluentes Químicos da Água/química
6.
Sci Total Environ ; 748: 141384, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-32823226

RESUMO

Multi-walled carbon nanotubes (MWCNTs) might induce the dysfunction of neuronal NO synthase (nNOS) and impair the function of brains. But to the best of our knowledge, this conclusion was made by using laboratory animals or conventional nerve cell cultures; however, these models might not reflect the complex conditions of human brains. Recently, the development of 3D brain organoids (also known as organotypic cultures) derived from human induced pluripotent stem cells (iPSCs) provides a platform to investigate the behaviors of human brains in vitro. In this study, we investigated the toxicity of MWCNTs to 3D brain organoids which expressed the cortical layer markers. It was shown that MWCNTs induced cytotoxicity to 3D brain organoids but not in dose-dependent manner. Exposure to high level of MWCNTs (64 µg/mL) reduced the levels of intracellular NO but increased superoxide. As the mechanism, 64 µg/mL MWCNTs significantly reduced the protein level of nNOS. The nNOS regulators nuclear factor kappa-B (NF-κB) proteins were significantly induced by MWCNTs, whereas Kruppel-like factor 4 (KLF4) proteins were reduced particularly after exposure to low level of MWCNTs (16 µg/mL). The results from fluorescence micro-optical sectioning tomography (MOST) confirmed the decrease of nNOS proteins, not only at the out-layers that directly contacted MWCNTs, but also at the inner-layers. Combined, our results suggested that MWCNTs could decrease nNOS activity by inducing oxidative stress and modulating NF-κB-KLF4 pathway. This study also showed the potential of 3D brain organoids in mechanism-based toxicology studies.


Assuntos
Células-Tronco Pluripotentes Induzidas , Nanotubos de Carbono , Animais , Encéfalo , Humanos , Nanotubos de Carbono/toxicidade , Organoides , Espécies Reativas de Oxigênio
7.
Toxicol Lett ; 332: 65-73, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32649966

RESUMO

Exposure to multi-walled carbon nanotubes (MWCNTs) might induce lipid droplet (LD) biogenesis, but the roles of physicochemical properties of MWCNTs, as well as the mechanisms, remain poorly understood. In this study, we investigated lipid laden foam formation in THP-1 macrophages exposed to MWCNTs of different diameters, and attempted transcriptomic analysis to study the possible mechanisms. We observed diameter-dependent cytotoxicity, lipid accumulation and intracellular reactive oxygen species production that were more pronounced for MWCNTs with smaller diameters compared with those with larger diameters. However, more MWCNTs with larger diameters were retained in macrophages after 24 h exposure. One possible explanation for the inverse relationship between MWCNT bio-effects and internalization is that macrophages altered the expression of exocytotic genes to export toxic MWCNTs. Transcriptomic data showed that MWCNTs with smaller diameters more effectively altered the expression of genes related with cytotoxicity and lipid metabolism, and KEGG pathway analysis suggested that MWCNTs with smaller diameters activated peroxisome proliferator-activated receptor (PPAR) signalling pathway (map03320), leading to over-expression of perilipin 2, the surface proteins of LDs. Western blot confirmed that MWCNTs effectively promoted CD36, PPARγ and perilipin 2, key components in map03320. Moreover, inhibition of PPARγ by chemicals or siRNA significantly inhibited lipid accumulation induced by MWCNTs with smaller diameters, and perilipin 2 proteins in MWCNT-exposed macrophages could be decreased by PPARγ siRNA. In conclusion, the results of this study revealed the induction of LDs by MWCNTs in a diameter-dependent manner through the activation of PPAR signalling pathway.


Assuntos
Gotículas Lipídicas/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Perfilação da Expressão Gênica , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Tamanho da Partícula , Receptores Ativados por Proliferador de Peroxissomo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Transcriptoma/efeitos dos fármacos
8.
Aquat Toxicol ; 225: 105546, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32574930

RESUMO

In natural environments, organisms are often exposed to several environmental pollutants at any one time, and the potential effects of such co-exposures on human and environmental health are of considerable concern. It is thought that multi-walled carbon nanotubes (MWCNTs) may interact with other pollutants in aquatic systems and induce considerably different effects compared with exposure to a single contaminant. The objective of this study was to evaluate the potential acute combined effects of mixtures of MWCNTs and 2,2',4,4'-tetrabromodiphenyl ether (BDE-47) on embryonic development stages, oxidative stress, apoptosis and DNA damage in developing zebrafish (Danio rerio). The embryos were treated with BDE-47 (5, 10, and 50 µg/L) and MWCNTs (50 mg/L), either combined or individually, for 96 h. Following exposure, BDE-47 induced significant acute toxicity, while the MWCNTs exhibited slight toxicity. When compared with BDE-47-only exposure, the inhibited growth induced by BDE-47 was weakened in the presence of MWCNTs. Similarly, the levels of oxidative stress biomarkers (reactive oxygen species, superoxide dismutase, catalase activities and malondialdehyde), apoptosis (apoptosis rate, caspase-3 and caspase-9 activities) and DNA damage (comet assay and comet olive tails) decreased in the presence of MWCNTs compared to those exposed to BDE-47 alone. These results demonstrate that MWCNTs can weaken the developmental inhibition, oxidative stress, apoptosis and DNA damage induced by BDE-47 in the early stages of zebrafish development.


Assuntos
Éteres Difenil Halogenados/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Apoptose/efeitos dos fármacos , Caspase 3 , Ensaio Cometa , Dano ao DNA , Humanos , Malondialdeído , Nanotubos de Carbono/toxicidade , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio , Superóxido Dismutase/metabolismo , Peixe-Zebra/embriologia
9.
Nanotoxicology ; 14(7): 929-946, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32538272

RESUMO

Multi-walled carbon nanotubes (MWCNTs) are known to induce pulmonary inflammatory effects through stimulating pro-inflammatory cytokine secretion from alveolar macrophages. Despite extensive studies on MWCNTs' pro-inflammatory reactivity, the understanding of molecular mechanisms involved is still incomplete. In this study, we investigated hemichannel's involvement in MWCNTs-induced macrophage IL-1ß release. Our results showed that the unmodified and COOH MWCNTs could induce ATP release and ATP-P2X7R axis-dependent IL-1ß secretion from THP-1 macrophages. By using various inhibitors, we confirmed that the MWCNTs-induced ATP release was primarily through hemichannels. EtBr dye uptake assay detected significant hemichannels opening in MWCNTs exposed THP-1 macrophages. Inhibition of hemichannels by CBX, 43Gap27, or 10Panx1 pretreatment results in decreased ATP and IL-1ß release. The addition of ATP restored the reduced IL-1ß secretion level from hemichannel inhibition. We also confirmed with five other types of MWCNTs that the induction of hemichannels by MWCNTs strongly correlates with their capacity to induce IL-1ß secretion. Taken together, we conclude that hemichannels-mediated ATP release and subsequent NLRP3 inflammasome activation through P2X7R may be one mechanism by which MWCNTs induce macrophage IL-1ß secretion. Our findings may provide a novel molecular mechanism for MWCNTs induced IL-1ß secretion.


Assuntos
Trifosfato de Adenosina/metabolismo , Conexinas/metabolismo , Interleucina-1beta/metabolismo , Macrófagos Alveolares/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Proteínas do Tecido Nervoso/metabolismo , Humanos , Inflamassomos/imunologia , Inflamassomos/metabolismo , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Nanotubos de Carbono/química , Células THP-1
10.
Nanotoxicology ; 14(8): 1017-1038, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32574508

RESUMO

Nanomaterials (NMs) with tubular structures, such as halloysite nanotubes (HNTs), have potential applications in biomedicine. Although the biocompatibility of HNTs has been investigated before, the toxicity of HNTs to blood vessels is rarely systemically evaluated. Herein, we compared the toxicity of HNTs and multi-walled carbon nanotubes (MWCNTs) to human umbilical vein endothelial cells (HUVECs) in vitro and blood vessels of mice in vivo. HUVECs internalized HNTs and MWCNTs, but the uptake of HNTs was not obviously changed by clathrin inhibitor. Exposure to NMs decreased cellular viability, activated apoptotic proteins and up-regulated adhesion molecules, including soluble vascular cell adhesion molecule 1 (sVCAM-1) and VCAM-1. As the mechanisms, NMs decreased NO levels, eNOS mRNA and eNOS/p-eNOS proteins. Meanwhile, NMs promoted intracellular ROS and autophagy dysfunction, shown as decreased protein levels of LC3, beclin-1 and ATG5. The eNOS regulator Kruppel-like factor 4 (KLF4) was inhibited, but another eNOS regulator KLF4 was surprisingly up-regulated. Under in vivo conditions, ICR mice intravenously injected with NMs (50 µg/mouse, once a day for 5 days) showed an increased percentage of neutrophils, monocytes and basophils. Meanwhile, autophagy dysfunction, eNOS uncoupling, activation of apoptotic proteins and alteration of KLF proteins were also observed in mouse aortas. All of the toxic effects were more pronounced for MWCNTs in comparison with HNTs based on the same mass concentrations. Our results may provide novel insights about the toxicity of NMs with tubular structures to blood vessels. Considering the toxicological data reported here, HNTs are probably safer nanocarriers compared with MWCNTs.


Assuntos
Aorta/efeitos dos fármacos , Argila/química , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Nanotubos/toxicidade , Animais , Aorta/metabolismo , Aorta/patologia , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Contagem de Células Sanguíneas , Técnicas de Cultura de Células , Sobrevivência Celular/efeitos dos fármacos , Células Cultivadas , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Humanos , Fatores de Transcrição Kruppel-Like/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Nanotubos/química , Nanotubos de Carbono/química , Óxido Nítrico Sintase Tipo III/metabolismo , Molécula 1 de Adesão de Célula Vascular/metabolismo
11.
Nanotoxicology ; 14(7): 947-967, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32574520

RESUMO

Multi-walled carbon nanotubes (MWCNTs) are one of the most widely used types of novel nano-fiber materials. The aim of this study was to establish an experimental system based on actual exposure dosage and environments and explore the roles and mechanisms of inflammation in the malignant transformation of pleural mesothelial cells induced by MWCNTs after low doses and long-term exposure. Here, we established an in vitro system by co-culturing macrophages and mesothelial cells and exposing these cells to high aspect ratio MWCNTs (0.1 µg/mL) for three months. Results indicated that IL-1ß, secreted by macrophages stimulated by MWCNTs, may significantly enhance the release of inflammatory cytokines, such as IL-8, TNF-α, and IL-6, from mesothelial cells. Results obtained from proliferation, migration, invasion, colony formation, and chromosomal aberration studies indicated that MWCNTs may promote malignant transformation of mesothelial cells after long-term and low-dose exposure via inflammation. Furthermore, the obtained results demonstrated that the NF-κB/IL-6/STAT3 pathway was active in the malignant transformation of Met 5A cells, induced by MWCNTs, and played an important role in the process. In conclusion, our results showed that the NF-κB (p65)/IL-6/STAT3 molecular pathway, which was mediated by inflammation, played an important role in the malignant transformation of pleural mesothelial cells induced by MWCNTs. These findings also provide novel ideas and references for the treatment of mesothelioma and offers options for the occupational safety of nanomaterial practitioners.


Assuntos
Proliferação de Células/efeitos dos fármacos , Citocinas/metabolismo , Células Epiteliais/efeitos dos fármacos , Neoplasias Pulmonares/imunologia , Macrófagos/efeitos dos fármacos , Mesotelioma/imunologia , Nanotubos de Carbono/toxicidade , Animais , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Movimento Celular/imunologia , Técnicas de Cocultura , Relação Dose-Resposta a Droga , Células Epiteliais/imunologia , Células Epiteliais/patologia , Técnicas de Silenciamento de Genes , Humanos , Inflamação , Interleucina-1beta/metabolismo , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Macrófagos/imunologia , Macrófagos/patologia , Mesotelioma/metabolismo , Mesotelioma/patologia , Células THP-1 , Fator de Transcrição RelA/genética , Fator de Transcrição RelA/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
12.
Ecotoxicol Environ Saf ; 202: 110892, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32593098

RESUMO

Carbon nanotubes presence in the environment increases every year because of exponential industrial production around the world. In aquatic environments, carbon nanotubes can interact with other pollutants based on their adsorbent surface chemistry properties. Heavy metal ions represent one of the biggest concerns in water resources nowadays due to anthropogenic activities, in which cadmium (Cd) is one of the most harmful metal for aquatic organisms. This study investigated the influence of two co-exposure protocols differing by the order of interaction of oxidized multiwalled carbon nanotubes (ox-MWCNT) with Cd in zebrafish liver cell line (ZFL). The ox-MWCNT was characterized, Cd content in culture medium and uptake by cells were quantified using ICP-MS and, the reactive oxygen species (ROS), the biotransformation enzymes activity of phase I and II as well as the antioxidants defenses and oxidative damage were analyzed. The effects on the cell cycle were investigated by flow cytometry and DNA damage by comet assay. The exposure to ox-MWCNT alone decreased the activity of catalase, glutathione peroxidase, and glutathione S-transferase and altered the cell cycle with a reduction of cells in the G2/M phase. Cd exposure alone decreased the activity of catalase and glutathione S-transferase, increased ROS, metallothionein, and lipid peroxidation content and causes genotoxicity in the cells. Despite different incubation protocol, the co-exposure ox-MWCNT-Cd increased the Cd content in ZFL cells after 24 h exposure, increased ROS production and DNA damage without differences between them. Our results showed the modulation of ox-MWCNT on Cd effects and contributed to future co-exposure toxicity investigations and nanosafety regulations involving carbon nanomaterials and aquatic pollutants.


Assuntos
Cádmio/toxicidade , Nanotubos de Carbono/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Antioxidantes/metabolismo , Catalase/metabolismo , Ciclo Celular , Linhagem Celular , Ensaio Cometa , Dano ao DNA , Glutationa Peroxidase/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Metais Pesados/farmacologia , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Testes de Toxicidade , Peixe-Zebra/metabolismo
13.
Chemosphere ; 257: 127205, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32502735

RESUMO

Multi-walled carbon nanotubes (MWCNTs), a common nanomaterial widely used and discharged in environment, might exert toxic effects on aquatic animals. In this paper, filter-feeding tadpole of Xenopus tropicalis was selected as bioindicator to study the exposure effects of MWCNTs suspensions of 0.5, 1, 2, 4 and 8 mg/L for 72 h. The results showed that the tadpoles could remain high survival rate of over 96.7% after 24 h's exposure to MWCNTs, but then decrease considerably, showing a significant time-dependent relationship. The LC50 was 2.53 mg/L for tadpoles exposed to MWCNTs for 72 h, when MWCNTs accumulated in their gills and digestive tracts. Moreover, the enrichment degree of MWCNTs in tadpole was related to exposure density than time. When MWCNTs suspension concentration was not over 1 mg/L, the heart rates increased significantly and then decreased continuously. The survivors from the toxicity test were transferred to fresh filtered water for recovery, but MWCNTs accumulated in the tadpoles' body didn't decrease obviously after 4 days. Although the maximum tadpoles survival rate of 80% was recorded in the exposure group of 0.5 mg/L MWCNTs, only 43.3% of the survivors could recover. Therefore, the final survival rate was negative related to the exposure densities of MWCNTs but positive related to the accumulating degree in tadpoles' body. The results demonstrated that MWCNTs exposure posed potential health risks to filter-feeding organisms by intake and accumulation in organs, which could provide useful information for the reasonable evaluation and scientific management of nanomaterials.


Assuntos
Nanotubos de Carbono/toxicidade , Xenopus/fisiologia , Animais , Brânquias/efeitos dos fármacos , Larva/efeitos dos fármacos
14.
Nanotoxicology ; 14(5): 711-724, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32374645

RESUMO

Prenatal particle exposure has been shown to increase allergic responses in offspring. Carbon nanotubes (CNTs) possess immunomodulatory properties, but it is unknown whether maternal exposure to CNTs interferes with offspring immune development. Here, C57Bl/6J female mice were intratracheally instilled with 67 of µg multiwalled CNTs on the day prior to mating. After weaning, tolerance and allergy responses were assessed in the offspring. Offspring of CNT-exposed (CNT offspring) and of sham-exposed dams (CTRL offspring) were intranasally exposed to ovalbumin (OVA) once weekly for 5 weeks to induce airway mucosal tolerance. Subsequent OVA sensitization and aerosol inhalation caused low or no OVA-specific IgE production and no inflammation. However, the CNT offspring presented with significantly lower OVA-specific IgG1 levels than CTRL offspring. In other groups of 5-week-old offspring, low-dose sensitization with OVA and subsequent OVA aerosol inhalation led to significantly lower OVA-specific IgG1 production in CNT compared to CTRL offspring. OVA-specific IgE and airway inflammation were non-significantly reduced in CNT offspring. The immunomodulatory effects of pre-gestational exposure to multiwalled CNTs were unexpected, but very consistent. The observations of suppressed antigen-specific IgG1 production may be of importance for infection or vaccination responses and warrant further investigation.


Assuntos
Formação de Anticorpos/efeitos dos fármacos , Antígenos/toxicidade , Hipersensibilidade/etiologia , Nanotubos de Carbono/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Animais , Antígenos/química , Feminino , Humanos , Hipersensibilidade/imunologia , Tolerância Imunológica/efeitos dos fármacos , Tolerância Imunológica/imunologia , Imunoglobulina G/sangue , Imunoglobulina G/imunologia , Inflamação , Exposição Materna/efeitos adversos , Camundongos , Camundongos Endogâmicos BALB C , Nanotubos de Carbono/química , Ovalbumina/imunologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/imunologia
15.
Toxicol Lett ; 328: 7-18, 2020 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-32311379

RESUMO

Multi-walled carbon nanotubes (MWCNT) are engineered nanomaterials widely used in industrial and biomedical applications. Yet, MWCNT inhalation may induce pulmonary adverse effects, and the MWCNT-7 (Mitsui-7) has been classified as possibly carcinogenic to humans. However, its molecular mechanisms of action are poorly understood and there are no biomarkers of exposure for occupational monitoring. Several pulmonary diseases, including lung cancer, have been associated with alterations in microRNA expression that are used as biomarkers of disease progression, and differentially-expressed microRNAs (DE miRNAs) can also allow understanding the molecular effects induced by a toxicant. In this study, we identify DE miRNAs in A549 alveolar epithelial cells following 24 h exposure to MWCNT-7 or crocidolite, as well as their enriched cellular functional pathways. These indicate that both materials change cell survival, differentiation and proliferative properties under the influence of AMPK, FoxO, TGF-ß and Hippo pathways, and their metabolic activity and cell-to-cell communication. In addition, MWCNT-7 affects the actin cytoskeleton, ubiquitin mediated proteolysis, and ECM-receptor interactions; crocidolite the PI3K-Akt and mTOR pathways, endocytosis, and central carbon metabolism. Since deregulation of these pathways may be related to carcinogenesis, an interaction network of DE miRNAs and corresponding target cancer-related genes was constructed, highlighting the carcinogenic potential of Mitsui-7.


Assuntos
Asbesto Crocidolita/toxicidade , Expressão Gênica/efeitos dos fármacos , MicroRNAs/genética , Nanotubos de Carbono/toxicidade , Alvéolos Pulmonares/efeitos dos fármacos , Células A549 , Carbono/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Alvéolos Pulmonares/metabolismo , Alvéolos Pulmonares/patologia
16.
Environ Int ; 139: 105672, 2020 06.
Artigo em Inglês | MEDLINE | ID: mdl-32248022

RESUMO

There are currently increasingly concerns over DNA damage related to free radicals due to their vital roles in human health, especially high-performance detection method. Herein, we report an ultra- sensitive monitoring of DNA damage associated with free radicals exposure using interdigitated electrode (IDE) array for the first time. The proposed IDE array was equipped with DNA-wrapped carbon nanotube-based bridges, which utilized the DNA damage mechanism due to the free radicals' attack and the efficient electrical detection nature of the interdigitated electrode. Experiments have been performed, and the results showed the device's capability for detecting DNA damage induced by multiple free radicals generated from different sources, including the Fenton reaction, UV radiation and cigarette smoke, showing the promising ability for DNA damage detection. In addition, the carbon nanotubes bridge-based interdigitated electrode sensor enabled different levels of sensing of DNA damage with great sensitivity and a wide detection range. It was illustrated that the ultrasensitive detection of free radicals generated from ultraviolet radiation (15 min - 125 min), cigarette smoke tar (1 µg/mL to 10 µg/mL) and Fenton reaction under different concentration of H2O2 (2.5 pM - 100 pM), have been detected successfully. Typically, the IDE array supports further performance improvement for the electrochemical detection in an ultrasensitive and high throughput route.


Assuntos
Técnicas Biossensoriais , Nanotubos de Carbono , Dano ao DNA , Eletrodos , Humanos , Peróxido de Hidrogênio , Nanotubos de Carbono/toxicidade , Raios Ultravioleta
18.
Environ Int ; 137: 105530, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32062310

RESUMO

INTRODUCTION: Inhalation of asbestos induces lung cancer via different cellular mechanisms. Together with the increased production of carbon nanotubes (CNTs) grows the concern about adverse effects on the lungs given the similarities with asbestos. While it has been established that CNT and asbestos induce epigenetic alterations, it is currently not known whether alterations at epigenetic level remain stable after withdrawal of the exposure. Identification of DNA methylation changes after a low dose of CNT and asbestos exposure and recovery can be useful to determine the fibre/particle toxicity and adverse outcome. METHODS: Human bronchial epithelial cells (16HBE) were treated with a low and non-cytotoxic dose (0.25 µg/ml) of multi-walled carbon nanotubes (MWCNTs-NM400) or single-walled carbon nanotubes (SWCNTs-SRM2483) and 0.05 µg/ml amosite (brown) asbestos for the course of four weeks (sub-chronic exposure). After this treatment, the cells were further incubated (without particle/fibre) for two weeks, allowing recovery from the exposure (recovery period). Nuclear depositions of the CNTs were assessed using femtosecond pulsed laser microscopy in a label-free manner. DNA methylation alterations were analysed using microarrays that assess more than 850 thousand CpG sites in the whole genome. RESULTS: At non-cytotoxic doses, CNTs were noted to be incorporated with in the nucleus after a four weeks period. Exposure to MWCNTs induced a single hypomethylation at a CpG site and gene promoter region. No change in DNA methylation was observed after the recovery period for MWCNTs. Exposure to SWCNTs or amosite induced hypermethylation at CpG sites after sub-chronic exposure which may involve in 'transcription factor activity' and 'sequence-specific DNA binding' gene ontologies. After the recovery period, hypermethylation and hypomethylation were noted for both SWCNTs and amosite. Hippocalcinlike 1 (HPCAL1), protease serine 3 (PRSS3), kallikrein-related peptidase 3 (KLK3), kruppel like factor 3 (KLF3) genes were hypermethylated at different time points in either SWCNT-exposed or amosite-exposed cells. CONCLUSION: These results suggest that the specific SWCNT (SRM2483) and amosite fibres studied induce hypo- or hypermethylation on CpG sites in DNA after very low-dose exposure and recovery period. This effect was not seen for the studied MWCNT (NM400).


Assuntos
Asbestos , Metilação de DNA , Nanotubos de Carbono , Asbestos/toxicidade , Brônquios , Células Epiteliais , Genes , Humanos , Pulmão , Nanotubos de Carbono/toxicidade , Tripsina
19.
J Nanobiotechnology ; 18(1): 36, 2020 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093716

RESUMO

Functionalized multi-walled carbon nanotubes (MWCNT) have become the focus of increased research interest, particularly in their application as tools in different areas, such as the biomedical field. Despite the benefits associated with functionalization of MWCNT, particularly in overcoming issues relating to solubility, several studies have demonstrated that these functionalized nanoparticles display different toxicity profiles. For this study, we aim to compare NR8383 cells responses to three well-characterized MWCNT with varying functional groups. This study employed cytotoxicity assays, transcriptomics and proteomics to assess their toxicity using NR8383 rat alveolar macrophages as an in vitro model. The study findings indicated that all MWCNT altered ribosomal protein translation, cytoskeleton arrangement and induced pro-inflammatory response. Only functionalized MWCNT alter mTOR signaling pathway in conjunction with increased Lamtor gene expression. Furthermore, the type of functionalization was also important, with cationic MWCNT activating the transcription factor EB and inducing autophagy while the anionic MWCNT altering eukaryotic translation initiation factor 4 (EIF4) and phosphoprotein 70 ribosomal protein S6 kinase (p70S6K) signaling pathway as well as upregulation Tlr2 gene expression. This study proposes that MWCNT toxicity mechanisms are functionalization dependent and provides evidence that inflammatory response is a key event of carbon nanotubes toxicity.


Assuntos
Perfilação da Expressão Gênica , Macrófagos Alveolares/efeitos dos fármacos , Nanotubos de Carbono/química , Nanotubos de Carbono/toxicidade , Animais , Autofagia , Cátions , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Expressão Gênica , L-Lactato Desidrogenase/metabolismo , Macrófagos Alveolares/metabolismo , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Nanoestruturas/química , Tamanho da Partícula , Proteômica , Ratos , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo
20.
Environ Res ; 183: 109219, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32085994

RESUMO

The Mixture exposure to pristine multi-walled carbon nanotubes (P-MWCNTs) and polycyclic aromatic hydrocarbons (PAHs) such as benzo α pyrene (BaP) in the environment is inevitable. Assessment toxicity of P-MWCNTs and BaP individually may not provide sufficient toxicological information. The objective of this work is to investigate the combined toxicity of P-MWCNTs and BaP in human epithelial lung cells (A549). The physico-chemical properties of P-MWCNTs were determined suing analytical instruments. The toxicity of P-MWCNTs and BaP on A549 lung cells individually or combined were assessed. For toxicity assessment, cell viability, ROS generation, oxidative DNA damage, and apoptosis experiments were conducted. The results of this study demonstrated that P-MWCNTs and BaP individually reduced cell viability in A549 lung cells, and oxidative stress was as the possible mechanism of cytotoxicity. The co-exposure to P-MWCNTs and BaP enhanced the cytotoxicity compared to exposure to P-MWCNTs and BaP individually, but not statistically significant. The two-factorial analysis demonstrated an additive toxicity interaction for co-exposure to P-MWCNTs and BaP. The complicated toxicity interaction among BaP with fibers and metal impurities of P-MWCNTS could be probable reasons for additive toxicity interaction. Results of this study could be helpful as the basis for future studies and risk assessment of co-exposure to MWCNTs and PAHs.


Assuntos
Benzo(a)pireno , Nanotubos de Carbono , Células A549 , Benzo(a)pireno/toxicidade , Sobrevivência Celular , Humanos , Pulmão/efeitos dos fármacos , Nanotubos de Carbono/toxicidade , Pirenos
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