Understanding the mechanism of silver nanoparticle toxicity

Abstract

The development of silver nanoparticles (AgNP) applications increasedthe concern about their toxicity. As the respiratory system in one of theexposure routes, the aim of this study was to evaluate the AgNP harmfuleffects developed in lung. AgNP were able to cleave H2O2 leading to OHproduction. In A549 cells exposed to 2.5 μg/mL AgNP a decreasedmitochondrial basal and maximal respiration (p<0.01) were observedafter 3h, while an increased H2O2 production was observed after 1h(p<0.001), which in turn, increased the 4-HNE (p<0.01) and HO-1(p<0.01) levels after 24h. In an EpiAirway 3D tissue AgNP exposuredecreased the transepithelial electrical resistance (p<0.05). In vivo AgNPeffects were evaluated using Balb/c mice instilled with 0.1 mg AgNP/kgbody weight. Biodistribution evaluation showed the lung as the mainorgan of AgNP deposition, where 1h after AgNP exposure tissue O2consumption increased (p<0.05) due to increased NOX activity (p<0.05)and increased mitochondrial respiration (p<0.001) mainly by increasedcomplex I activity (p<0.01). Mitochondrial H2O2 production rateincreased (p<0.05) along with increased antioxidant enzymes activity(p<0.01) and decreased GSH/GSSG ratio. These results show that AgNPpresence in the lung may lead to oxidative damage and impairedepithelial function due to O2 metabolism alterations.