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.

银纳米粒子 (AgNPs) 是最常用的纳米粒子 (NPs)，因为它们具有抗微生物特性，而肺系统为这些用于雾化产品的 NPs 提供了主要的入口。AgNPs 有可能引起肺毒性，穿过肺泡-毛细血管屏障，并在肺部暴露后分布到远程器官。然而，AgNPs（继发于肺暴露）对主要器官（包括肝脏、脾脏、肾脏和大脑）的影响的潜在机制仍不完全清楚。本研究的目的是分析在不同时间点（1 天和 7 天），不同涂层（聚乙烯吡咯烷酮和柠檬酸盐）的单剂量 5 mg/kg AgNPs（10 nm）肺部暴露的器官毒性和分布。 Balb/C 小鼠。银离子（Ag ⁺) 用作离子对照。对于两种类型的 AgNP，在肺部均观察到炎症的组织学证据。在暴露于 AgNPs 的动物中，包括肿瘤坏死因子 α (TNF-α) 和白细胞介素 6 (IL-6) 在内的炎症标志物在肺、脑和肝中显着增加。银⁺离子引起脾脏和肾脏中TNF-α和IL-6的显着增加。在大多数研究的器官中观察到还原型谷胱甘肽、一氧化氮和 8-异前列腺素的显着增加。此外，AgNPs 在肺、肝和脑中诱导 DNA 损伤和细胞凋亡。生物分布表明，AgNPs主要分布于脾、肝、肺，肾和脑中分布较少。相比之下，暴露后 7 天在大多数器官中检测到 Ag 的量减少，但肾脏和大脑中的 AgAc 除外。总之，肺部暴露于 AgNPs 会导致氧化应激标志物、炎症、DNA 损伤和远程器官的生物分布。这些发现为肺暴露于 AgNPs 的病理生理效应和组织分布提供了新的机制见解。