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1.
Environ Toxicol Pharmacol ; 86: 103654, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-33823299

RESUMEN

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.


Asunto(s)
Células Epiteliales Alveolares/efectos de los fármacos , Nanopartículas/toxicidad , Proteína A Asociada a Surfactante Pulmonar/antagonistas & inhibidores , Titanio/toxicidad , Óxido de Zinc/toxicidad , Células A549 , Células Epiteliales Alveolares/metabolismo , Supervivencia Celular/efectos de los fármacos , Citocinas/metabolismo , Humanos , Inflamación/inducido químicamente , Inflamación/metabolismo , Pulmón , Proteína A Asociada a Surfactante Pulmonar/metabolismo , Especies Reactivas de Oxígeno/metabolismo
2.
Toxicol Lett ; 190(2): 179-86, 2009 Oct 28.
Artículo en Inglés | MEDLINE | ID: mdl-19619626

RESUMEN

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.


Asunto(s)
Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Fluoruros/farmacología , Actinas/biosíntesis , Actinas/genética , Animales , Western Blotting , Adhesión Celular/efectos de los fármacos , Recuento de Células , Línea Celular Tumoral , Colorantes , Citoesqueleto/efectos de los fármacos , Citoesqueleto/metabolismo , Citoesqueleto/ultraestructura , ADN de Neoplasias/biosíntesis , Relación Dosis-Respuesta a Droga , Proteínas de Neoplasias/biosíntesis , Proteínas de Neoplasias/metabolismo , Fosforilación , Prolactina/metabolismo , Ratas , Sales de Tetrazolio , Tiazoles
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