The respiratory tract is the route of entry for accidentally inhaled AgNPs, which can reach the lungs and redistribute to other main organs through systemic circulation. In the present work, we aimed to evaluate silver biodistribution and biological effects after 1 or 2 intratracheal instillations (IT) of two differently sized PVP-coated AgNPs (5 and 50 nm-3 mg/kg) and ionic silver (AgNO3-1 mg/kg bw) in mice. Furthermore, nuclear magnetic resonance (NMR) metabolomics was applied to unveil pulmonary metabolic variations. Animals exposed to 5 nm AgNP (AgNP5) showed higher levels of ionic silver in organs, especially in the lung, spleen, kidney and liver, while animals exposed to 50 nm AgNP (AgNP50) showed higher levels of silver in the blood. Animals exposed to AgNP50 excreted higher amounts of silver than those exposed to AgNP5, which is consistent with higher tissue accumulation of silver in animals exposed to the latter. Lung metabolic profiling revealed several Ag-induced alterations in metabolites involved in different pathways, such as glycolysis and tricarboxylic acid (TCA) cycle, amino acid and phospholipid metabolism, and antioxidant defense. Notably, most of the metabolic changes observed after 1 IT were absent in animals subjected to 2 IT of AgNO3, or reversed for AgNPs, suggesting adaptation mechanisms to cope with the initial insult and recover homeostasis. Graphical abstract.

中文翻译：

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急性气管内滴注后，纳米银颗粒在小鼠体内的生物分布和肺代谢作用。

呼吸道是意外吸入的AgNPs的进入途径，该AgNPs可以到达肺部并通过系统循环重新分布到其他主要器官。在目前的工作中，我们旨在评估两种不同大小的PVP包覆的AgNP（5和50 nm-3 mg / kg）和离子银（AgNO3-1 mg）经1或2次气管内滴注（IT）后的银生物分布和生物学效应。 / kg bw）。此外，核磁共振（NMR）代谢组学被用于揭示肺部代谢变化。暴露于5 nm AgNP（AgNP5）的动物器官中，尤其是肺，脾，肾和肝中离子银的含量较高，而暴露于50 nm AgNP（AgNP50）的动物血液中的银含量更高。暴露于AgNP50的动物排泄的银量高于暴露于AgNP5的动物，这与暴露于后者的动物体内较高的银组织积累相一致。肺部代谢分析显示，银诱导的代谢产物的改变涉及不同途径，例如糖酵解和三羧酸（TCA）循环，氨基酸和磷脂代谢以及抗氧化防御。值得注意的是，在接受1 IT的AgNO3的动物中不存在观察到的大多数代谢变化，或对AgNPs逆转的动物没有这种代谢变化，这表明适应机制可以应对最初的伤害并恢复体内平衡。图形概要。和抗氧化防御。值得注意的是，在接受1 IT的AgNO3的动物中不存在观察到的大多数代谢变化，或对AgNPs逆转的动物没有这种代谢变化，这表明适应机制可以应对最初的伤害并恢复体内平衡。图形概要。和抗氧化防御。值得注意的是，在接受1 IT的AgNO3的动物中不存在观察到的大多数代谢变化，或对AgNPs逆转的动物没有这种代谢变化，这表明适应机制可以应对最初的伤害并恢复体内平衡。图形概要。