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1.
Environ Toxicol Pharmacol ; 86: 103654, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33823299

RESUMO

The increasing use of metal oxide nanoparticles (MONPs) as TiO2 NPs or ZnO NPs has led to environmental release and human exposure. The respiratory system, effects on lamellar bodies and surfactant protein A (SP-A) of pneumocytes, can be importantly affected. Exposure of human alveolar epithelial cells (A549) induced differential responses; a higher persistence of TiO2 in cell surface and uptake (measured by Atomic Force Microscopy) and sustained inflammatory response (by means of TNF-α, IL-10, and IL-6 release) and ROS generation were observed, whereas ZnO showed a modest response and low numbers in cell surface. A reduction in SP-A levels at 24 h of exposure to TiO2 NPs (concentration-dependent) or ZnO NPs (the higher concentration) was also observed, reversed by blocking the inflammatory response (by the inhibition of IL-6). Loss of SP-A represents a relevant target of MONPs-induced inflammatory response that could contribute to cellular damage and loss of lung function.


Assuntos
Células Epiteliais Alveolares/efeitos dos fármacos , Nanopartículas/toxicidade , Proteína A Associada a Surfactante Pulmonar/antagonistas & inibidores , Titânio/toxicidade , Óxido de Zinco/toxicidade , Células A549 , Células Epiteliais Alveolares/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocinas/metabolismo , Humanos , Inflamação/induzido quimicamente , Inflamação/metabolismo , Pulmão , Proteína A Associada a Surfactante Pulmonar/metabolismo , Espécies Reativas de Oxigênio/metabolismo
2.
Toxicol Lett ; 190(2): 179-86, 2009 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-19619626

RESUMO

The consumption of drinking water rich in fluoride has toxic effects on the central nervous system. In cell biology research, fluoride is currently used as a phosphatase inhibitor. The aim of the present study was to evaluate the effect of fluoride on different physiological processes in GH4C1 pituitary tumour cells. We used a range of different fluoride concentrations, from levels below normal human serum concentrations (0.23 and 1.2 micromol/L) to those observed in chronically exposed persons (10.7 micromol/L) and above (107 and 1072 micromol/L). Treatment of 10.7 micromol/L fluoride resulted in a discrete induction of DNA synthesis, without a change in cell number. Cell migration, a behaviour stimulated by growth factors, was increased in cells treated with 2.4 micromol/L. At this fluoride concentration, changes in phosphorylation status of both cytoskeletal and cytosolic protein fractions, as well as in actin cytoskeletal arrangements were observed. The GH4C1 fluoride treated cells had significantly less cellular protein than control cells, suggesting an effect of fluoride on hormone secretion and protein synthesis in this endocrine cell. The bioreduction of MTT was significantly increased with a wide range of fluoride concentrations. With the highest fluoride concentration, 1072 micromol/L, all of the analysed parameters were significantly reduced, suggesting that this dose is highly toxic in GH4C1 cells. Our results show that biologically relevant concentrations of fluoride are capable of increasing cell migration in tumour cells, suggesting that exposure to fluoride could stimulate tumour invasion.


Assuntos
Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Fluoretos/farmacologia , Actinas/biossíntese , Actinas/genética , Animais , Western Blotting , Adesão Celular/efeitos dos fármacos , Contagem de Células , Linhagem Celular Tumoral , Corantes , Citoesqueleto/efeitos dos fármacos , Citoesqueleto/metabolismo , Citoesqueleto/ultraestrutura , DNA de Neoplasias/biossíntese , Relação Dose-Resposta a Droga , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/metabolismo , Fosforilação , Prolactina/metabolismo , Ratos , Sais de Tetrazólio , Tiazóis
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