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1.
Colloids Surf B Biointerfaces ; 172: 152-160, 2018 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-30172199

RESUMO

Due to unique optical and electronic properties tin oxide nanoparticles (SnO2 NPs) have shown potential for various applications including solar cell, catalyst, and biomedicine. However, there is limited information concerning the interaction of SnO2 NPs with human cells. In this study, we explored the potential mechanisms of cytotoxicity of SnO2 NPs in human breast cancer (MCF-7) cells. Results demonstrated that SnO2 NPs induce cell viability reduction, lactate dehydrogenase leakage, rounded cell morphology, cell cycle arrest and low mitochondrial membrane potential in dose- and time-dependent manner. SnO2 NPs were also found to provoke oxidative stress evident by generation of reactive oxygen species (ROS), hydrogen peroxide (H2O2) and lipid peroxidation, while depletion of glutathione (GSH) level and lower activity of several antioxidant enzymes. Remarkably, we observed that ROS generation, GSH depletion, and cytotoxicity induced by SnO2 NPs were effectively abrogated by antioxidant N-acetylcycteine. Our data have shown that SnO2 NPs induce toxicity in MCF-7 cells via oxidative stress. This study warrants further research to explore the genotoxicity of SnO2 NPs in different types of cancer cells.


Assuntos
Neoplasias da Mama/patologia , Nanopartículas/toxicidade , Estresse Oxidativo/efeitos dos fármacos , Compostos de Estanho/toxicidade , Acetilcisteína/farmacologia , Antioxidantes/metabolismo , Apoptose/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Feminino , Humanos , L-Lactato Desidrogenase/metabolismo , Células MCF-7 , Nanopartículas/ultraestrutura , Oxidantes/toxicidade
2.
Toxicol Sci ; 164(2): 501-511, 2018 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-29722875

RESUMO

Tin sulfide (SnS2) nanoflowers (NFs) with highly photocatalytic activity for wastewater treatment may lead to potential health hazards via oral routes of human exposure. No studies have reported the hepatic effects of SnS2 NFs on the metabolic function and hepatotoxicity. In this study, we examined the hepatic effects of the oral administration of SnS2 NFs (250-1000 mg/kg) to ICR mice for 14 days, with the particle size ranging from 50 to 200 nm. Serum and liver tissue samples were assayed using biochemical analysis, liver histopathology and metabolic gene expression. The different sizes of SnS2 NFs (250 mg/kg dose), such as 50, 80, and 200 nm, did not induce any adverse hepatic effect related to biochemical parameters or histopathology in the treated mice compared with controls. The oral administration of 50-nm SnS2 NFs at doses of 250, 500, and 1000 mg/kg for 14 days produced dose-dependent hepatotoxicity and inflammatory responses in treated mice. Furthermore, the expression of metabolic genes in the liver tissues was altered, supporting the SnS2 NF-related hepatotoxic phenotype. The oral administration of SnS2 NFs also produced abnormal microstructures in the livers of the treated mice. Taken together, these data indicate that the increased risk of hepatotoxicity in SnS2 NF-treated mice was independent of the particle size but was dependent on their dose. The no-observed-adverse effect level was <250 mg/kg for the 50-nm SnS2 NFs. Our study provides an experimental basis for the safe application of SnS2 NFs.


Assuntos
Doença Hepática Induzida por Substâncias e Drogas/etiologia , Fígado/efeitos dos fármacos , Nanoestruturas/toxicidade , Sulfetos/toxicidade , Compostos de Estanho/toxicidade , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Administração Oral , Animais , Apoptose/efeitos dos fármacos , Proteínas de Transporte/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/sangue , Doença Hepática Induzida por Substâncias e Drogas/patologia , Relação Dose-Resposta a Droga , Fígado/metabolismo , Fígado/patologia , Masculino , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos ICR , Nanoestruturas/administração & dosagem , Tamanho da Partícula , Distribuição Aleatória , Sulfetos/administração & dosagem , Sulfetos/sangue , Compostos de Estanho/administração & dosagem , Compostos de Estanho/sangue
3.
Food Chem Toxicol ; 118: 264-271, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29772267

RESUMO

Indium tin oxide (ITO) is widely used as a transparent conducting electrode in photoelectron devices. Because ITO production has soared, the potential health hazards caused by occupational exposure to this material have attracted much attention. However, little is known about the mechanisms of the toxic action of ITO nanoparticles (NPs). The present study was designed to examine the genotoxic mechanisms of ITO NPs using human lung epithelial A549 cells. We found that exposing A549 cells to ITO NPs triggered the intracellular accumulation of ITO NPs, the generation of reactive oxygen species (ROS), and the induction of DNA damage. Treatment of the cells with N-acetyl-l-cysteine (NAC), an ROS quenching agent, decreased intracellular ROS levels but not DNA damage, indicating that the genotoxic effect of ITO NPs is not mediated by intracellular ROS. Interestingly, treatment with ammonium chloride, a lysosomotropic agent, decreased intracellular solubility of ITO NPs and attenuated DNA damage. Nuclear accumulation of indium ions in ITO-NP-exposed cells was confirmed by inductively coupled plasma-mass spectrometry. Our results indicate that the ITO-NP-mediated genotoxicity is caused by indium ions that are solubilized in the acidic lysosomal condition and accumulated in the nucleus where they damage DNA, without the involvement of ROS.


Assuntos
Nanopartículas Metálicas/toxicidade , Mutagênicos/toxicidade , Espécies Reativas de Oxigênio/metabolismo , Compostos de Estanho/toxicidade , Células A549 , Dano ao DNA , Humanos , Microscopia Eletrônica de Transmissão , Testes de Mutagenicidade
4.
Artigo em Inglês | MEDLINE | ID: mdl-29775400

RESUMO

Tin dioxide nanofibers (SnDNFs) are small fibers that have many applications. Tin dioxide nanofibers can be used in cosmetics, solar cells, toxic gas release sensors, and air pollution control. To date there have been few studies on the cytotoxicity of SnDNFs. The goal of this research is to determine if electrospun SnDNFs are toxic in a lung cancer cell line (A549). Considering the nano-scale size of the fibers, they can easily be inhaled and enter the pulmonary system and cause toxic effects in the lung. Occupational exposure to SnDNFs has been linked to pulmonary disease, making the A549 cell line important in this study. Nanofiber toxicity can vary based upon the characteristics of the fibers. Smaller nanofibers have been shown to have more toxic effects than their larger counterparts. The synthesized SnDNFs were characterized using SEM, Raman spectroscopy, and powder X-ray diffractometer (PXRD). SEM images showed the fibers to be 200-300 nm in diameter. Raman spectroscopy and PXRD indicated that the fibers were in the rutile phase. After quantifying the SnDNFs, the fibers were introduced to A549 cells at concentrations ranging from 0.02-500 µg mL-1 and incubated at 37°C. These cells were quantified with the MTT assay to measure cell proliferation (IC50 = 0.02 mg mL-1), while lactate dehydrogenase (LDH) leakage was used to determine cytotoxicity, and apoptosis assays to assess the mechanism of cell death. Increasing concentration of SnDNF generated a consequential decrease in cell proliferation and viability. The percent cytotoxicity of SnDNF was not significantly changed at the various concentrations and time frames. In order to gain additional insight about the mechanism of cytotoxicity of SnDNFs, genes with links to inflammation and apoptosis were evaluated and found to be over-expressed in treated cells. At the concentrations of SnDNF examined, SnDNF was mildly toxic to the A549 cells.


Assuntos
Apoptose/efeitos dos fármacos , Nanofibras/toxicidade , Compostos de Estanho/toxicidade , Células A549 , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Expressão Gênica/efeitos dos fármacos , Humanos , Teste de Materiais , Exposição Ocupacional/efeitos adversos , Exposição Ocupacional/análise , Testes de Toxicidade
5.
Arch Toxicol ; 92(4): 1349-1361, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29484482

RESUMO

Occupational exposure to indium tin oxide (ITO) particles has been associated with the development of severe lung diseases, including pulmonary alveolar proteinosis (PAP). The mechanisms of this lung toxicity remain unknown. Here, we reveal the respective roles of resident alveolar (Siglec-Fhigh AM) and recruited interstitial (Siglec-Flow IM) macrophages contributing in concert to the development of PAP. In mice treated with ITO particles, PAP is specifically associated with IL-1α (not GM-CSF) deficiency and Siglec-Fhigh AM (not Siglec-Flow IM) depletion. Mechanistically, ITO particles are preferentially phagocytosed and dissolved to soluble In3+ by Siglec-Flow IM. In contrast, Siglec-Fhigh AM weakly phagocytose or dissolve ITO particles, but are sensitive to released In3+ through the expression of the transferrin receptor-1 (TfR1). Blocking pulmonary Siglec-Flow IM recruitment in CCR2-deficient mice reduces ITO particle dissolution, In3+ release, Siglec-Fhigh AM depletion, and PAP formation. Restoration of IL-1-related Siglec-Fhigh AM also prevented ITO-induced PAP. We identified a new mechanism of secondary PAP development according to which metal ions released from inhaled particles by phagocytic IM disturb IL-1α-dependent AM self-maintenance and, in turn, alveolar clearance.


Assuntos
Macrófagos Alveolares/imunologia , Macrófagos/imunologia , Proteinose Alveolar Pulmonar/imunologia , Compostos de Estanho/toxicidade , Animais , Humanos , Interleucina-1alfa/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Exposição Ocupacional , Fagocitose , Proteinose Alveolar Pulmonar/induzido quimicamente , Receptores da Transferrina/metabolismo
6.
Toxicol Sci ; 161(2): 388-400, 2018 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-29069489

RESUMO

SnS2 nanoflowers (SnS2 NFs) have been widely used in photoelectric and catalytic applications. However, its explosure and reproductive toxicity is unknown. The aim of this study was to investigate the effect of exposure to 3 different sized-SnS2 flowers (dose: 38 mg/kg; size: 50, 80, and 200 nm) in testes of mice for 4 weeks by intraperitoneal injection. Though the body weight of mice treated or not with SnS2 NFs was not different, and SnS2 NFs were distributed to the organs including liver, kidney, spleen, heart, brain, and testis, more distribution SnS2 NFs (50 and 80 nm) were found in testicle tissues compared with SnS2 flowers (200 nm) in those tissues. The results of sperm count and survival analysis, histopathological evaluation, and qRT-PCR detection showed that there was moderate reproductive toxicity induced by the small-sized SnS2 NFs in testicle tissues. Furthermore, elevated malondialdehyde level and decreased superoxide dismutase activity were also observed in the SnS2 NFs (dose: 38 mg/kg; size: 50 and 80 nm) treated groups. Likewise, the qRT-PCR data indicated that SnS2 NFs can induce apoptosis and inflammation responses. Although the pro-inflammation marker of TNF-α, IL-1ß, iNOS, and COX-2 at the mRNA levels were higher expression in 50 and 80 nm groups than that in control and 200 nm group, no statistical significance existed between 50 and 80 nm groups. Accordingly, the repeated-dose toxicity of SnS2 NFs in testicle tissues was also observed in a dose-dependent manner by intraperitoneal injection of SnS2 NFs (size: 50 nm; 0.38, 3.8, and 38 mg/kg) for 4 weeks, when determined by sperm count, survival rate, and qRT-PCR analysis. In addition, transmission electron microscopy showed that the ultrastructural abnormalities formed by the small-sized SnS2 NFs in testes were more severe than those formed by the large-sized SnS2 in testes. Taken together, these findings implied that the SnS2 NFs activated inflammation responses that signified apoptosis in murine testes. This study provided useful information for risk analysis and regulation of SnS2 NFs by administration agencies.


Assuntos
Apoptose/efeitos dos fármacos , Nanoestruturas/toxicidade , Sulfetos/toxicidade , Testículo/efeitos dos fármacos , Compostos de Estanho/toxicidade , Animais , Ciclo-Oxigenase 2/genética , Citocinas/genética , Relação Dose-Resposta a Droga , Expressão Gênica/efeitos dos fármacos , Injeções Intraperitoneais , Masculino , Camundongos Endogâmicos ICR , Nanoestruturas/química , Óxido Nítrico Sintase Tipo II/genética , Tamanho da Partícula , Contagem de Espermatozoides , Sulfetos/química , Propriedades de Superfície , Testículo/metabolismo , Testículo/ultraestrutura , Compostos de Estanho/química , Distribuição Tecidual
7.
Toxicol Appl Pharmacol ; 331: 85-93, 2017 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-28552777

RESUMO

Indium-tin oxide (ITO) is used to produce flat panel displays and several other technology products. Composed of 90% indium oxide (In2O3) and 10% tin oxide (SnO2) by weight, ITO is synthesized under conditions of high heat via a process known as sintering. Indium lung disease, a recently recognized occupational illness, is characterized by pulmonary alveolar proteinosis, fibrosis, and emphysema. Murine macrophage (RAW 264.7) and epidermal (JB6) cells stably transfected with AP-1 to study tumor promoting potential, were used to differentiate between the toxicological profiles of sintered ITO (SITO) and unsintered mixture (UITO). We hypothesized that sintering would play a key role in free radical generation and cytotoxicity. Exposure of cells to both UITO and SITO caused a time and dose dependent decrease of the viability of cells. Intracellular ROS generation was inversely related to the dose of both UITO and SITO, a direct reflection of the decreased number of viable RAW 264.7 and JB6/AP-1 cells observed at higher concentrations. Electron spin resonance showed significantly increased hydroxyl radical (OH) generation in cells exposed to UITO compared to SITO. This is different from LDH release, which showed that SITO caused significantly increased damage to the cell membrane compared to UITO. Lastly, the JB6/AP-1 cell line did not show activation of the AP-1 pathway. Our results highlight both the differences in the mechanisms of cytotoxicity and the consistent adverse effects associated with UITO and SITO exposure.


Assuntos
Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Epiderme/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Compostos de Estanho/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/fisiologia , Dano ao DNA/fisiologia , Relação Dose-Resposta a Droga , Epiderme/metabolismo , Macrófagos/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo
8.
Chemosphere ; 165: 33-40, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27639075

RESUMO

Semiconductor SnO2 nanoparticles (NPs) are being exploited for various applications, including those in the environmental context. However, toxicity studies of SnO2 NPs are very limited. This study evaluated the toxic effect of two sizes of spherical SnO2 NPs (2 and 40 nm) and one size of flower-like SnO2 NPs (800 nm) towards the environmental bacteria E. coli and B. subtilis. SnO2 NPs were synthesized using a hydrothermal or calcination method and they were well characterized prior to toxicity assessment. To evaluate toxicity, cell viability and membrane damage were determined in cells (1 × 109 CFU mL-1) exposed to up to 1000 mg L-1 of NPs, using the plate counting method and confocal laser scanning microscopy. Spherical NPs of smaller primary size (E2) had the lowest hydrodynamic size (226 ± 96 nm) and highest negative charge (-30.3 ± 10.1 mV). Smaller spherical NPs also showed greatest effect on viability (IC50 > 500 mg L-1) and membrane damage of B. subtilis, whereas E. coli was unaffected. Scanning electron microscopy confirmed the membrane damage of exposed B. subtilis and also exhibited the attachment of E2 NPs to the cell surface, as well as the elongation of cells. It was also apparent that toxicity was caused solely by NPs, as released Sn4+ was not toxic to B. subtilis. Thus, surface charge interaction between negatively charged SnO2 NPs and positively charged molecules on the membrane of the Gram positive B. subtilis was indicated as the key mechanism related to toxicity of NPs.


Assuntos
Bacillus subtilis/crescimento & desenvolvimento , Membrana Celular/efeitos dos fármacos , Escherichia coli/crescimento & desenvolvimento , Nanopartículas Metálicas/toxicidade , Compostos de Estanho/toxicidade , Bacillus subtilis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Microscopia Eletrônica de Varredura , Tamanho da Partícula
9.
Swiss Dent J ; 126(6): 566-572, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27377293

RESUMO

Stannous chloride (SnCl(2), 35%) can increase microtensile bond strength between a self-etching adhesive and dental hard tissue either alone or in combination with phosphoric acid (H(3)PO(4), 35%). Whereas cell toxicity of H(3)PO(4) has been sufficiently investigated, little is known about the toxicity of concentrated SnCl(2). The present study determined the in vitro toxicity of SnCl(2), H(3)PO(4), the primer of a self-etching adhesive (Clearfil SE) and combinations thereof at three concentrations (0.01%–0.3%) in a L929 fibroblast bioassay. Cell viability was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, the integrity of cell membranes was visualised by trypan blue staining (cell necrosis assay). Cell viability was impaired at concentrations between 0.09% and 0.13% for SnCl(2), between 0.06% and 0.09% for H(3)PO(4), and between 0.19% and 0.29% for Clearfil SE primer. Combinations of agents showed additive toxic effects. SnCl(2) showed a slightly lower but comparable in vitro toxicity to H(3)PO(4), which gives a perspective for further in vitro, in situ and clinical studies on this issue, and for the intraoral use of SnCl(2) to increase bond strength between an adhesive system and both enamel and dentine.


Assuntos
Condicionamento Ácido do Dente , Bioensaio , Sobrevivência Celular/efeitos dos fármacos , Ácidos Fosfóricos/toxicidade , Cimentos de Resina/toxicidade , Compostos de Estanho/toxicidade , Linhagem Celular , Combinação de Medicamentos , Humanos , Técnicas In Vitro
10.
Environ Toxicol Pharmacol ; 45: 282-94, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27343753

RESUMO

Indium tin oxide (ITO) is a technologically important semiconductor. An increasing number of cases of severe lung effects (characterized by pulmonary alveolar proteinosis and/or interstitial fibrosis) in ITO-exposed workers warrants a review of the toxicological hazards. Short- and long-term inhalation studies in rats and mice revealed persistent alveolar proteinosis, inflammation and fibrosis in the lungs down to concentrations as low as 0.01mg/m(3). In rats, the incidences of bronchiolo-alveolar adenomas and carcinomas were significantly increased at all concentrations. In mice, ITO was not carcinogenic. A few bronchiolo-alveolar adenomas occurring after repeated intratracheal instillation of ITO to hamsters have to be interpreted as treatment-related. In vitro and in vivo studies on the formation of reactive oxygen species suggest epigenetic effects as cause of the lung tumor development. Repeated intratracheal instillation of ITO to hamsters slightly affected the male sexual organs, which might be interpreted as a secondary effect of the lung damage. Epidemiological and medical surveillance studies, serum/blood indium levels in workers as well as data on the exposure to airborne indium concentrations indicate a need for measures to reduce exposure at ITO workplaces.


Assuntos
Poluentes Atmosféricos/toxicidade , Pulmão/efeitos dos fármacos , Mutagênicos/toxicidade , Compostos de Estanho/toxicidade , Animais , Feminino , Fertilidade/efeitos dos fármacos , Humanos , Exposição por Inalação/efeitos adversos , Masculino , Semicondutores , Testes de Toxicidade/métodos
11.
Toxicol Ind Health ; 32(9): 1720-8, 2016 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-25907664

RESUMO

In this study, the mutagenicity and genotoxicity of indium tin oxide (ITO) nanomaterial were assessed using two standard genotoxicity assays, the Salmonella reverse mutation assay (Ames test) and the in vitro micronucleus (MN) assay. Seven different concentrations (12.5, 25, 50, 75, 100, 125, and 150 µg/plate) of this nanomaterial were tested using the Ames test on the TA98 and TA100 strains in the presence and absence of the S9 mixture. At all the concentrations tested, this substance did not significantly increase the number of revertant colonies compared with the control with or without S9 mixture. The genotoxic effects of ITO were investigated in human peripheral lymphocytes treated with 125, 250, 500, and 750 µg/ml concentrations of this substance for 24- and 48-h treatment periods using an MN test. Nuclear division index (NDI) was also calculated in order to determine the cytotoxicity of ITO. It was determined that ITO increased MN frequency in the 750 µg/ml concentration in 24- and 48-h treatments. In addition, ITO dose dependently decreased the NDI significantly for two treatment periods.


Assuntos
Carcinógenos Ambientais/toxicidade , Divisão do Núcleo Celular/efeitos dos fármacos , Linfócitos/efeitos dos fármacos , Nanopartículas Metálicas/toxicidade , Micronúcleos com Defeito Cromossômico/induzido quimicamente , Salmonella typhimurium/efeitos dos fármacos , Compostos de Estanho/toxicidade , Adulto , Animais , Carcinógenos Ambientais/química , Células Cultivadas , Feminino , Humanos , Linfócitos/citologia , Linfócitos/imunologia , Masculino , Nanopartículas Metálicas/química , Testes para Micronúcleos , Microssomos Hepáticos/enzimologia , Microssomos Hepáticos/metabolismo , Mutagênese/efeitos dos fármacos , Testes de Mutagenicidade , Tamanho da Partícula , Ratos Sprague-Dawley , Salmonella typhimurium/metabolismo , Compostos de Estanho/química , Compostos de Estanho/metabolismo , Adulto Jovem
12.
J Appl Toxicol ; 36(4): 618-26, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26472246

RESUMO

Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. Occupational exposures to potentially toxic particles generated during ITO production have increased in recent years as the demand for consumer electronics continues to rise. Previous studies have demonstrated cytotoxicity in vitro and animal models have shown pulmonary inflammation and injury in response to various indium-containing particles. In humans, pulmonary alveolar proteinosis (PAP) and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which indium materials or specific processes in the workplace may be the most toxic to workers is unknown. Here we examined the pulmonary toxicity of three different particle samples that represent real-life worker exposures, as they were collected at various production stages throughout an ITO facility. Indium oxide (In2O3), sintered ITO (SITO) and ventilation dust (VD) particles each caused pulmonary inflammation and damage in rats over a time course (1, 7 and 90 days post-intratracheal instillation), but SITO and VD appeared to induce greater toxicity in rat lungs than In2O3 at a dose of 1 mg per rat. Downstream pathological changes such as PAP and fibrosis were observed in response to all three particles 90 days after treatment, with a trend towards greatest severity in animals exposed to VD when comparing animals that received the same dose. These findings may inform workplace exposure reduction efforts and provide a better understanding of the pathogenesis of an emerging occupational health issue.


Assuntos
Poluentes Atmosféricos/toxicidade , Pneumonia/patologia , Compostos de Estanho/toxicidade , Animais , Lavagem Broncoalveolar , Relação Dose-Resposta a Droga , Poeira , Concentração de Íons de Hidrogênio , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Masculino , Fagocitose , Pneumonia/induzido quimicamente , Ratos , Ratos Sprague-Dawley , Fator de Necrose Tumoral alfa/metabolismo
13.
J Photochem Photobiol B ; 151: 17-24, 2015 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-26143160

RESUMO

A number of different nanomaterials produced and incorporated into various products are rising. However, their environmental hazards are frequently unknown. Here we consider three different metal oxide compounds (SnO2, In2O3, and Al2O3), which have not been extensively studied and are expected to have low toxicity. This study aimed to comprehensively characterize the physicochemical properties of these nanomaterials and investigate their toxicity on bacteria (Escherichia coli) under UV illumination and in the dark, as well as on a marine diatom (Skeletonema costatum) under ambient illumination/dark (16-8h) cycles. The material properties responsible for their low toxicity have been identified based on comprehensive experimental characterizations and comparison to a metal oxide exhibiting significant toxicity under illumination (anatase TiO2). The metal oxide materials investigated exhibited significant difference in surface properties and interaction with the living organisms. In order for a material to exhibit significant toxicity, it needs to be able to both form a stable suspension in the culture medium and to interact with the cell walls of the test organism. Our results indicated that the observed low toxicities of the three nanomaterials could be attributed to the limited interaction between the nanoparticles and cell walls of the test organisms. This could occur either due to the lack of significant attachment between nanoparticles and cell walls, or due to their tendency to aggregate in solution.


Assuntos
Parede Celular/efeitos dos fármacos , Nanopartículas Metálicas/química , Nanopartículas Metálicas/toxicidade , Óxido de Alumínio/toxicidade , Antibacterianos/farmacologia , Antibacterianos/toxicidade , Membrana Celular/efeitos dos fármacos , Parede Celular/química , Diatomáceas/efeitos dos fármacos , Ecotoxicologia/métodos , Espectroscopia de Ressonância de Spin Eletrônica , Escherichia coli/efeitos dos fármacos , Escherichia coli/efeitos da radiação , Índio/toxicidade , Lipopolissacarídeos/química , Microscopia Eletrônica de Transmissão , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Compostos de Estanho/toxicidade , Titânio/toxicidade , Raios Ultravioleta
14.
PLoS One ; 10(4): e0124368, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25874458

RESUMO

Indium-tin oxide (ITO) is used to make transparent conductive coatings for touch-screen and liquid crystal display electronics. As the demand for consumer electronics continues to increase, so does the concern for occupational exposures to particles containing these potentially toxic metal oxides. Indium-containing particles have been shown to be cytotoxic in cultured cells and pro-inflammatory in pulmonary animal models. In humans, pulmonary alveolar proteinosis and fibrotic interstitial lung disease have been observed in ITO facility workers. However, which ITO production materials may be the most toxic to workers and how they initiate pulmonary inflammation remain poorly understood. Here we examined four different particle samples collected from an ITO production facility for their ability to induce pro-inflammatory responses in vitro. Tin oxide, sintered ITO (SITO), and ventilation dust particles activated nuclear factor kappa B (NFκB) within 3 h of treatment. However, only SITO induced robust cytokine production (IL-1ß, IL-6, TNFα, and IL-8) within 24 h in both RAW 264.7 mouse macrophages and BEAS-2B human bronchial epithelial cells. Our lab and others have previously demonstrated SITO-induced cytotoxicity as well. These findings suggest that SITO particles activate the NLRP3 inflammasome, which has been implicated in several immune-mediated diseases via its ability to induce IL-1ß release and cause subsequent cell death. Inflammasome activation by SITO was confirmed, but it required the presence of endotoxin. Further, a phagocytosis assay revealed that pre-uptake of SITO or ventilation dust impaired proper macrophage phagocytosis of E. coli. Our results suggest that adverse inflammatory responses to SITO particles by both macrophage and epithelial cells may initiate and propagate indium lung disease. These findings will provide a better understanding of the molecular mechanisms behind an emerging occupational health issue.


Assuntos
Indústria Química , Células Epiteliais/efeitos dos fármacos , Inflamassomos/agonistas , Macrófagos/efeitos dos fármacos , Exposição Ocupacional , Compostos de Estanho/toxicidade , Animais , Proteínas de Transporte/genética , Proteínas de Transporte/imunologia , Linhagem Celular , Endotoxinas/farmacologia , Células Epiteliais/citologia , Células Epiteliais/imunologia , Escherichia coli/imunologia , Regulação da Expressão Gênica , Humanos , Inflamassomos/genética , Inflamassomos/imunologia , Interleucina-1beta , Interleucina-6/genética , Interleucina-6/imunologia , Interleucina-8/genética , Interleucina-8/imunologia , Macrófagos/citologia , Macrófagos/imunologia , Camundongos , NF-kappa B/genética , NF-kappa B/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR , Tamanho da Partícula , Fagocitose/efeitos dos fármacos , Transdução de Sinais , Compostos de Estanho/química , Compostos de Estanho/classificação , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/imunologia
15.
Metallomics ; 7(5): 816-27, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25781390

RESUMO

Indium tin oxide (ITO) is widely used in liquid crystal displays (LCDs) or plasma and mobile phone displays. Elevated production and usage of ITO in such displays have led to increased concerns over the safety of industrial workers exposed to particulate aerosols produced during cutting, grinding and polishing of these materials. However, the cellular effects of ITO nanoparticles (NPs) are still unclear, although it has been reported that micro-scale ITO particles induce cytotoxicity. The aim of this study was to examine the potential of ITO NPs to induce cytotoxicity, oxidative stress, and DNA damage using human lung adenocarcinoma A549 cells. Here, stable dispersions of a medium containing ITO NPs were obtained using pre-adsorption and centrifugal fractionation methods, and the A549 cells were incubated in this medium. The ITO NPs showed low cytotoxic effects as shown by the WST-1 and LDH assays. Transmission electron microscopy observations showed the cellular uptake of ITO NPs. The ITO NPs increased the intracellular level of reactive oxygen species and the expression of the heme oxygenase 1 gene. Further, the results of alkaline comet assays showed that ITO NPs induced DNA damage. Thus, these results suggest that ITO NPs possess a genotoxic potential on human lung adenocarcinoma A549 cells.


Assuntos
Adenocarcinoma/patologia , Neoplasias Pulmonares/patologia , Pulmão/efeitos dos fármacos , Mutagênicos/toxicidade , Nanopartículas/toxicidade , Compostos de Estanho/toxicidade , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma de Pulmão , Linhagem Celular Tumoral , Dano ao DNA/efeitos dos fármacos , Humanos , Pulmão/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo
16.
Toxicol Sci ; 144(1): 17-26, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25527823

RESUMO

Macrophage-solubilized indium-containing particles (ICPs) were previously shown in vitro to be cytotoxic. In this study, we compared macrophage solubilization and cytotoxicity of indium phosphide (InP) and indium-tin oxide (ITO) with similar particle diameters (∼ 1.5 µm) and then determined if relative differences in these in vitro parameters correlated with pulmonary toxicity in vivo. RAW 264.7 macrophages were treated with InP or ITO particles and cytotoxicity was assayed at 24 h. Ionic indium was measured in 24 h culture supernatants. Macrophage cytotoxicity and particle solubilization in vitro were much greater for InP compared with ITO. To correlate changes in vivo, B6C3F1 mice were treated with InP or ITO by oropharyngeal aspiration. On Days 14 and 28, bronchoalveolar lavage (BAL) and pleural lavage (PL) fluids were collected and assayed for total leukocytes. Cell differentials, lactate dehydrogenase activity, and protein levels were also measured in BAL. All lavage parameters were greatly increased in mice treated with InP compared with ITO. These data suggest that macrophage solubilization and cytotoxicity of some ICPs in vitro are capable of predicting pulmonary toxicity in vivo. In addition, these differences in toxicity were observed despite the two particulate compounds containing similar amounts of indium suggesting that solubilization, not total indium content, better reflects the toxic potential of some ICPs. Soluble InCl3 was shown to be more cytotoxic than InP to macrophages and lung epithelial cells in vitro further suggesting that ionic indium is the primary cytotoxic component of InP.


Assuntos
Poluentes Ocupacionais do Ar/toxicidade , Índio/toxicidade , Pneumopatias/induzido quimicamente , Macrófagos/efeitos dos fármacos , Fagocitose , Fosfinas/toxicidade , Compostos de Estanho/toxicidade , Poluentes Ocupacionais do Ar/química , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/citologia , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Índio/química , Exposição por Inalação , L-Lactato Desidrogenase/metabolismo , Leucócitos/efeitos dos fármacos , Leucócitos/metabolismo , Pneumopatias/metabolismo , Pneumopatias/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Tamanho da Partícula , Fosfinas/química , Células RAW 264.7 , Solubilidade , Fatores de Tempo , Compostos de Estanho/química
17.
Arch Toxicol ; 89(12): 2345-54, 2015 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-25253649

RESUMO

Brominated flame retardants such as tetrabromobisphenol-A (TBBPA) may exert (developmental) neurotoxic effects. However, data on (neuro)toxicity of halogen-free flame retardants (HFFRs) are scarce. Recent in vitro studies indicated a high neurotoxic potential for some HFFRs, e.g., zinc stannate (ZS), whereas the neurotoxic potential of other HFFRs, such as aluminum diethylphosphinate (Alpi), appears low. However, the in vivo (neuro)toxicity of these compounds is largely unknown. We therefore investigated effects of neonatal exposure to TBBPA, Alpi or ZS on synaptic plasticity in mouse hippocampus. Male C57bl/6 mice received a single oral dose of 211 µmol/kg bw TBBPA, Alpi or ZS on postnatal day (PND) 10. On PND 17-19, effects on hippocampal synaptic plasticity were investigated using ex vivo extracellular field recordings. Additionally, we measured levels of postsynaptic proteins involved in long-term potentiation (LTP) as well as flame retardant concentrations in brain, muscle and liver tissues. All three flame retardants induced minor, but insignificant, effects on LTP. Additionally, TBBPA induced a minor decrease in post-tetanic potentiation. Despite these minor effects, expression of selected synaptic proteins involved in LTP was not affected. The flame retardants could not be measured in significant amounts in the brains, suggesting low bioavailability and/or rapid elimination/metabolism. We therefore conclude that a single neonatal exposure on PND 10 to TBBPA, Alpi or ZS does affect neurodevelopment and synaptic plasticity only to a small extent in mice. Additional data, in particular on persistence, bioaccumulation and (in vivo) toxicity, following prolonged (developmental) exposure are required for further (human) risk assessment.


Assuntos
Retardadores de Chama/toxicidade , Potenciação de Longa Duração/efeitos dos fármacos , Plasticidade Neuronal/efeitos dos fármacos , Síndromes Neurotóxicas/etiologia , Fatores Etários , Alumínio/farmacologia , Alumínio/toxicidade , Animais , Animais Recém-Nascidos , Disponibilidade Biológica , Retardadores de Chama/farmacocinética , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteínas do Tecido Nervoso/metabolismo , Síndromes Neurotóxicas/fisiopatologia , Compostos Organofosforados/farmacologia , Compostos Organofosforados/toxicidade , Bifenil Polibromatos/farmacocinética , Bifenil Polibromatos/toxicidade , Compostos de Estanho/farmacocinética , Compostos de Estanho/toxicidade , Distribuição Tecidual
18.
Appl Biochem Biotechnol ; 175(3): 1567-75, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25410804

RESUMO

In this paper, we have established for the first time, the terrific efficiency of aqueous extract of agricultural waste dried peel of sugar apple (Annona squamosa) in the rapid synthesis of stable SnO2 nanoparticles. In topical years, the deployment of secondary metabolites from plant extract has emerged as a novel technology for the synthesis of various nanoparticles. In this paper, we have studied the potential of SnO2 nanoparticles assembly using agricultural waste source for the first time. The synthesized nanoparticles were characterized and confirmed as SnO2 nanoparticles by using UV-visible spectroscopy, XRD, and TEM analysis. The motivation of this study was to examine cytotoxicity study of SnO2 nanoparticles against hepatocellular carcinoma cell line (HepG2). SnO2 nanoparticles inhibited the cell proliferation in a dose- and time-dependent manner with an IC50 value of 148 µg/mL. The treated cells showed an altered morphology with increasing concentrations of SnO2 nanoparticles. Our result shows that the SnO2 nanoparticles exhibit moderate cytotoxicity towards the hepatocellular carcinoma (HepG2) at tested concentrations.


Assuntos
Annona/química , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Nanopartículas/toxicidade , Compostos de Estanho/toxicidade , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Forma Celular/efeitos dos fármacos , Cristalização , Humanos , Nanopartículas Metálicas/ultraestrutura , Tamanho da Partícula , Extratos Vegetais/química , Espectrofotometria Ultravioleta , Difração de Raios X
19.
Ann Am Thorac Soc ; 11(9): 1395-403, 2014 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25295756

RESUMO

RATIONALE: Occupational exposure to indium compounds, including indium-tin oxide, can result in potentially fatal indium lung disease. However, the early effects of exposure on the lungs are not well understood. OBJECTIVES: To determine the relationship between short-term occupational exposures to indium compounds and the development of early lung abnormalities. METHODS: Among indium-tin oxide production and reclamation facility workers, we measured plasma indium, respiratory symptoms, pulmonary function, chest computed tomography, and serum biomarkers of lung disease. Relationships between plasma indium concentration and health outcome variables were evaluated using restricted cubic spline and linear regression models. MEASUREMENTS AND MAIN RESULTS: Eighty-seven (93%) of 94 indium-tin oxide facility workers (median tenure, 2 yr; median plasma indium, 1.0 µg/l) participated in the study. Spirometric abnormalities were not increased compared with the general population, and few subjects had radiographic evidence of alveolar proteinosis (n = 0), fibrosis (n = 2), or emphysema (n = 4). However, in internal comparisons, participants with plasma indium concentrations ≥ 1.0 µg/l had more dyspnea, lower mean FEV1 and FVC, and higher median serum Krebs von den Lungen-6 and surfactant protein-D levels. Spline regression demonstrated nonlinear exposure response, with significant differences occurring at plasma indium concentrations as low as 1.0 µg/l compared with the reference. Associations between health outcomes and the natural log of plasma indium concentration were evident in linear regression models. Associations were not explained by age, smoking status, facility tenure, or prior occupational exposures. CONCLUSIONS: In indium-tin oxide facility workers with short-term, low-level exposure, plasma indium concentrations lower than previously reported were associated with lung symptoms, decreased spirometric parameters, and increased serum biomarkers of lung disease.


Assuntos
Dispneia/epidemiologia , Volume Expiratório Forçado , Mucina-1/sangue , Exposição Ocupacional/efeitos adversos , Proteína D Associada a Surfactante Pulmonar/sangue , Compostos de Estanho/sangue , Capacidade Vital , Adulto , Asma/epidemiologia , Biomarcadores/sangue , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Exposição Ocupacional/análise , Proteinose Alveolar Pulmonar/diagnóstico por imagem , Radiografia , Sons Respiratórios , Espirometria , Compostos de Estanho/toxicidade , Estados Unidos/epidemiologia
20.
J Toxicol Environ Health A ; 77(20): 1193-209, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25208660

RESUMO

Occupational exposure to indium compound particles has recently been associated with lung disease among workers in the indium-tin oxide (ITO) industry. Previous studies suggested that excessive alveolar surfactant and reactive oxygen species (ROS) may play a role in the development of pulmonary lesions following exposure to indium compounds. However, toxicity at the cellular level has not been comprehensively evaluated. Thus, the aim of this study was to assess which, if any, compounds encountered during ITO production are toxic to cultured cells and ultimately contribute to the pathogenesis of indium lung disease. The compounds used in this study were collected from eight different processing stages at an ITO production facility. Enhanced dark field imaging showed 5 of the compounds significantly associated with cells within 1 h, suggesting that cellular reactions to the compound particles may be occurring rapidly. To examine the potential cytotoxic effects of these associations, ROS generation, cell viability, and apoptosis were evaluated following exposures in RAW 264.7 mouse monocyte macrophage and BEAS-2B human bronchial epithelial cell lines. Both exhibited reduced viability with exposures, while apoptosis only occurred in RAW 264.7 cells. Our results suggested that excessive ROS production is likely not the predominant mechanism underlying indium-induced lung disease. However, the effects on cell viability reveal that several of the compounds are cytotoxic, and therefore, exposures need to be carefully monitored in the industrial setting.


Assuntos
Pneumopatias/patologia , Pulmão/efeitos dos fármacos , Exposição Ocupacional/análise , Compostos de Estanho/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Ensaio Cometa , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/patologia , Humanos , Pulmão/citologia , Pulmão/patologia , Pneumopatias/induzido quimicamente , Macrófagos/citologia , Macrófagos/efeitos dos fármacos , Macrófagos/patologia , Metalurgia , Camundongos , Tamanho da Partícula , Espécies Reativas de Oxigênio/metabolismo
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