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Silver nanoparticles and silver ions cause inflammatory response through induction of cell necrosis and the release of mitochondria in vivo and in vitro

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Abstract

Owing to the excellent antibacterial and antiviral activity, silver nanoparticles have a widespread use in the food and pharmaceutical industries. With the increase in the production and use of the related products, the potential hazard of silver nanoparticles has aroused public attention. The main purpose of this study is to explore the toxicity of silver nanoparticles and induction of lung inflammation in vitro and in vivo. Here, we validated that small amounts of silver ions dissolved from silver nanoparticles caused the depolarization of plasma membrane, resulting in an overload of intracellular sodium and calcium, and eventually led to the cell necrosis. The blockers of calcium or sodium channels inversed the toxicity of silver ions. Then, we instilled silver nanoparticles or silver nitrate (50 μg per mouse) into the lungs of mice, and this induced pulmonary injury and mitochondrial content release, led to the recruitment of neutrophils to the lung tissue via p38 MAPK pathway. Altogether, these data show that released silver ions from nanoparticles induced cell necrosis through Na+ and Ca2+ influx and triggered pulmonary inflammation through elevating mitochondrial-related contents released from these necrotic cells.

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Funding

This work is supported by the National Major Scientific and Technological Special Project for “Significant New Drugs Development” (No. 2018ZX09733001), National Natural Science Foundation Regional Innovation and Development (U19A2003), the Excellent Youth Foundation of Sichuan Scientific Committe Grant in China (No.2019JDJQ008) and by the Development Program of  China (No.2016YFA0201402).

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  1. Lu Li and Zhenfei Bi contributed equally to this work.

Authors and Affiliations

  1. Laboratory of Aging Research and Cancer Drug Target, State Key Laboratory of Biotherapy and Cancer Center, National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, No. 17, Block 3, Southern Renmin Road, Chengdu, Sichuan, 610041, People’s Republic of China

    Lu Li, Zhenfei Bi, Yuzhu Hu, Lu Sun, Yanlin Song, Siyuan Chen, Fei Mo, Jingyun Yang, Yuquan Wei & Xiawei Wei

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  1. Lu Li
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Li, L., Bi, Z., Hu, Y. et al. Silver nanoparticles and silver ions cause inflammatory response through induction of cell necrosis and the release of mitochondria in vivo and in vitro. Cell Biol Toxicol 37, 177–191 (2021). https://doi.org/10.1007/s10565-020-09526-4

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