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1.
ACS Nano ; 8(12): 12098-109, 2014 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-25415137

RESUMO

We investigated the effect of large (40 nm) graphene quantum dots (GQDs) in concanavalin A (Con A; 12 mg/kg i.v.)-induced mouse hepatitis, a T cell-mediated liver injury resembling fulminant hepatitis in humans. Intravenously injected GQDs (50 mg/kg) accumulated in liver and reduced Con A-mediated liver damage, as demonstrated by histopathological analysis and a decrease in liver lipid peroxidation and serum levels of liver transaminases. The cleavage of apoptotic markers caspase-3/PARP and mRNA levels of proapoptotic mediators Puma, Noxa, Bax, Bak1, Bim, Apaf1, and p21, as well as LC3-I conversion to autophagosome-associated LC3-II and expression of autophagy-related (Atg) genes Atg4b, Atg7, Atg12, and beclin-1, were attenuated by GQDs, indicating a decrease in both apoptosis and autophagy in the liver tissue. This was associated with the reduced liver infiltration of immune cells, particularly the T cells producing proinflammatory cytokine IFN-γ, and a decrease in IFN-γ serum levels. In the spleen of GQD-exposed mice, mRNA expression of IFN-γ and its transcription factor T-bet was reduced, while that of the IL-33 ligand ST2 was increased. The hepatoprotective effect of GQDs was less pronounced in ST2-deficient mice, indicating that it might depend on ST2 upregulation. In vitro, GQDs inhibited splenocyte IFN-γ production, reduced the activation of extracellular signal-regulated kinase in macrophage and T cell lines, inhibited macrophage production of the free radical nitric oxide, and reduced its cytotoxicity toward hepatocyte cell line HepG2. Therefore, GQDs alleviate immune-mediated fulminant hepatitis by interfering with T cell and macrophage activation and possibly by exerting a direct hepatoprotective effect.


Assuntos
Grafite/química , Grafite/farmacologia , Hepatite/tratamento farmacológico , Hepatite/imunologia , Tamanho da Partícula , Pontos Quânticos/química , Animais , Apoptose/efeitos dos fármacos , Transporte Biológico , Biomarcadores/metabolismo , Linhagem Celular , Concanavalina A/efeitos adversos , Citoproteção/efeitos dos fármacos , Regulação da Expressão Gênica/efeitos dos fármacos , Grafite/metabolismo , Grafite/uso terapêutico , Hepatite/metabolismo , Hepatite/patologia , Humanos , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Estresse Oxidativo/efeitos dos fármacos
2.
Biomaterials ; 35(15): 4428-35, 2014 May.
Artigo em Inglês | MEDLINE | ID: mdl-24612819

RESUMO

Synthesis of new antibacterial agents is becoming increasingly important in light of the emerging antibiotic resistance. In the present study we report that electrochemically produced graphene quantum dots (GQD), a new class of carbon nanoparticles, generate reactive oxygen species when photoexcited (470 nm, 1 W), and kill two strains of pathogenic bacteria, methicillin-resistant Staphylococcus aureus and Escherichia coli. Bacterial killing was demonstrated by the reduction in number of bacterial colonies in a standard plate count method, the increase in propidium iodide uptake confirming the cell membrane damage, as well as by morphological defects visualized by atomic force microscopy. The induction of oxidative stress in bacteria exposed to photoexcited GQD was confirmed by staining with a redox-sensitive fluorochrome dihydrorhodamine 123. Neither GQD nor light exposure alone were able to cause oxidative stress and reduce the viability of bacteria. Importantly, mouse spleen cells were markedly less sensitive in the same experimental conditions, thus indicating a fairly selective antibacterial photodynamic action of GQD.


Assuntos
Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Grafite/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Fármacos Fotossensibilizantes/farmacologia , Pontos Quânticos/química , Animais , Antibacterianos/química , Células Cultivadas , Escherichia coli/metabolismo , Infecções por Escherichia coli/tratamento farmacológico , Grafite/química , Humanos , Luz , Staphylococcus aureus Resistente à Meticilina/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Estresse Oxidativo/efeitos dos fármacos , Fármacos Fotossensibilizantes/química , Espécies Reativas de Oxigênio/metabolismo , Infecções Estafilocócicas/tratamento farmacológico
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