Remote effects and biodistribution of pulmonary instilled silver nanoparticles in mice

Silver nanoparticles (AgNPs) are the most commonly used nanoparticles (NPs) owing to their anti-microbial properties, and the pulmonary system provides a major portal of entry for these NPs used in aerosolized products. AgNPs have the potential to cause pulmonary toxicity, cross the alveolar-capillary barrier, and distribute to remote organs following pulmonary exposure. The mechanism underlying the effects of AgNPs, secondary to lung exposure, on the major organs including liver, spleen, kidney and brain, however, is still not completely understood. The aim of this study was to analyze the organ toxicity and distribution of pulmonary exposure to single dose of 5 mg/kg AgNPs (10 nm) with varying coatings (polyvinylpyrrolidone and citrate), at different time points (1 and 7 days), in Balb/C mice. Silver ions (Ag⁺) were used as ionic control. Histological evidence of inflammation was observed in lungs for both types of AgNPs. Markers of inflammation including tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) were significantly increased in lung, brain and liver in AgNPs exposed animals. Ag⁺ ions caused significant increase of TNF-α and IL-6 in the spleen and kidney. Significant increase of reduced glutathione, nitric oxide, and 8-isoprostane was observed in most of the organs investigated. Furthermore, AgNPs induced DNA damage and apoptosis in the lung, liver and brain. The biodistribution showed that, AgNPs were distributed mainly in the spleen, liver, lung and little in kidney and brain. Comparatively, reduced amount of Ag was detected in most organs 7 days after exposure, except for AgAc in the kidney and brain. In conclusion, pulmonary exposure to AgNPs caused oxidative stress markers, inflammation, DNA damage and biodistribution in remote organs. These findings provide a novel mechanistic insight into the pathophysiological effects and tissue distribution of lung exposure to AgNPs.