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1.
Colloids Surf B Biointerfaces ; 140: 104-116, 2016 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-26741270

RESUMO

Graphene and its derivatives have garnered significant scientific interest and have potential use in nano-electronics as well as biomedicine. However the undesirable biological consequence, especially upon inhalation of the particle, requires further investigations. This study aimed to elucidate the nano-biointeractions of PEGylated reduced graphene oxide (PrGO) and reduced graphene oxide (rGO) with that of lung alveolar epithelial cells (A549). Both nanomaterials showed dose dependent decrease in cell viability and alteration of cell morphology after 24h. Upon intracellular uptake of PrGO, it elicited oxidative stress mediated apoptosis in the cells by inducing ROS, loss of mitochondrial membrane potential (MMP) and inflammatory response by NF-κB activation. Conversely, rGO was found to scavenge ROS efficiently except at high dose after 24h. It was found that ROS at high dose of rGO prompted loss of MMP. rGO was found to adhere to the cell membrane, where it is assumed to bind to cell surface Toll like receptors (TLRs) thereby activating NF-κB mediated inflammatory response. All these events culminated in an increase in apoptosis of A549 cells after 24h of rGO exposure. It was also noticed that both the nanomaterials did not initiate lysosomal pathway but instead activated mitochondria mediated apoptosis. This study highlights the possible adverse toxic effect of PrGO and rGO upon inhalation and persistence of these particles in the lungs. Further research is required to comprehend the biological response of PrGO and rGO so as to advance its biomedical application and safety.


Assuntos
Células Epiteliais Alveolares/metabolismo , Grafite/química , Nanoestruturas/química , Óxidos/química , Polietilenoglicóis/química , Células Epiteliais Alveolares/efeitos dos fármacos , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Grafite/farmacocinética , Grafite/farmacologia , Humanos , Pulmão/citologia , Lisossomos/efeitos dos fármacos , Lisossomos/metabolismo , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , NF-kappa B/metabolismo , Nanoestruturas/ultraestrutura , Oxirredução , Óxidos/farmacocinética , Óxidos/farmacologia , Espécies Reativas de Oxigênio/metabolismo , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
2.
Colloids Surf B Biointerfaces ; 112: 204-12, 2013 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-23988777

RESUMO

The aim of the study was to evaluate the cells-nanoparticle interactions and molecular toxicity after delayed hypersensitivity in Guinea pigs, exposed to hydroxyapatite nanoparticles (HANP). The study focuses on synthesizing and characterizing HANPs and gaining an insight into the cytotoxicity, molecular toxicity, hypersensitivity and oxidative stress caused by them in vitro and in vivo. HANP was synthesized by chemical method and characterized by standard methods. Cytotoxicity was assessed on L929 cells by MTT assay and in vitro studies were carried out on rat liver homogenate. In vivo study was carried out by topical exposure of Guinea pigs with HANP, repeatedly, and evaluating the skin sensitization potential, blood parameters, oxidative stress in liver and brain and DNA damage (8-hydroxyl-2-deoxyguanosine: 8-OHdG) in liver. The results of the study indicated that there was no cytotoxicity (up to 600µg/mL) and oxidative damage (up to 100µg/mL), when exposed to HANPs. It was also evident that, there was no skin sensitization and oxidative damage when HANP were exposed to Guinea pigs.


Assuntos
Durapatita/toxicidade , Hipersensibilidade Tardia/induzido quimicamente , Nanopartículas/toxicidade , Animais , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Dano ao DNA , Durapatita/química , Durapatita/imunologia , Cobaias , Peroxidação de Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Fígado/metabolismo , Camundongos , Microscopia Eletrônica de Varredura , Nanopartículas/química , Nanopartículas/ultraestrutura , Nanotecnologia , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Pele/efeitos dos fármacos , Pele/imunologia
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