Local Administration of Gold Nanoparticles Prevents Pivotal Pathological Changes in Murine Models of Atopic Asthma.
Although gold nanoparticles have been shown to exhibit a range of beneficial biological properties, including antiinflammatory and anti-oxidant effects, their putative impact on allergic asthma has not been addressed. In this study, we evaluated the potential of nasal-instilled gold nanoparticles to prevent allergen-induced asthma in distinct murine models of this disease. Swiss-Webster (outbred) and A/J (inbred) mice were sensitized with ovalbumin and then treated with intranasal injections of gold nanoparticles (6 and 60 μg/kg), 1 h before ovalbumin challenges. Lung function, leukocyte infiltration, mucus exacerbation, extracellular matrix deposition, cytokine generation and oxidative stress were evaluated 24 h after the last challenge. In both mice strains, gold nanoparticles clearly inhibited (70-100%) allergen-induced accumulation of inflammatory cells as well as the production of both pro-inflammatory cytokines and reactive oxygen species. In A/J mice, recognized as genetic asthma prone animals, instilled gold nanoparticles clearly prevented mucus production, peribronchiolar fibrosis and airway hyper-reactivity triggered by allergen provocation. In conclusion, these findings demonstrate that gold nanoparticles prevented pivotal features of asthma, including airway hyper-reactivity, inflammation and lung remodelling. Such protective effects are accounted for by reduction in lung tissue generation of pro-inflammatory cytokines and chemokines, in a mechanism probably related to down-regulation in the levels of oxidative stress.
Emiliano
E
Barreto
Magda Fraguas
MF
Serra
Rafael Vital
RV
Dos Santos
Cássio Eráclito Alves
CE
Dos Santos
Jandir
J
Hickmann
Amanda Costa
AC
Cotias
Camila Ribeiro Rodrigues
CR
Pão
Suelen Gauna
SG
Trindade
Vanessa
V
Schimidt
Cristian
C
Giacomelli
Vinicius Frias
VF
Carvalho
Patricia Machado
PM
Rodrigues E Silva
Renato Sérgio Balão
RS
Cordeiro
Marco Aurélio
MA
Martins
D000818:Animals; D001249:Asthma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control*; D004195:Disease Models, Animal; D018450:Disease Progression; D006046:Gold / Q000008:administration & dosage*; D015552:Injections, Intralesional; D008297:Male; D053768:Metal Nanoparticles / Q000008:administration & dosage*; D051379:Mice; D020556:Neutrophil Infiltration; D011014:Pneumonia / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D017382:Reactive Oxygen Species / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism
D017382:Reactive Oxygen Species; D017392:Thiobarbituric Acid Reactive Substances; D006046:Gold