Mechanisms of toxicity of amorphous silica nanoparticles on human lung submucosal cells in vitro: protective effects of fisetin.
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McCarthy J, Inkielewicz-Stepniak I, Corbalan JJ, Radomski MW
Mechanisms of toxicity of amorphous silica nanoparticles on human lung submucosal cells in vitro: protective effects of fisetin.
Chem Res Toxicol. 2012 Oct 15;25(10):2227-35. doi: 10.1021/tx3002884. Epub 2012 Sep 19.
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- 22931364 [ View in PubMed]
- Abstract
There is growing evidence that amorphous silica nanoparticles (SiO(2)-NP) can cause an inflammatory response in the lung. We studied in vitro the effects of exposing human lung submucosal cells to SiO(2)-NP of various sizes (10, 150, and 500 nm) for 2-24 h. Cell survival, reactive oxygen species (ROS), malondialdehyde (MDA) levels, cytokine production, inflammatory gene expression, and genotoxicity were measured after exposure of Calu-3 cells to 10SiO(2)-NP in the presence or absence of the flavanoid fisetin and an antioxidant enzyme catalase. The exposure of Calu-3 cells to 10SiO(2)-NP resulted in (1) increased cytotoxicity and cell death in a time- and concentration-dependent manner, with a lethal concentration (LC(5)(0)) of 9.7 mug/mL after 24 h; (2) enhanced gene expression of interleukin (IL)-6, IL-8, and matrix metalloproteinase-9; (3) a significant correlation between increases in MDA and cytotoxicity at 18 h; (4) ROS production; (5) IL-6 and IL-8 release; and (6) up-regulation of the pro-apoptotic genes, p53 and caspase-3. Cell death and inflammatory reactions were attenuated by fisetin and catalase. We observed that 150- and 500SiO(2)-NP exerted no toxic effects on Calu-3 cells. In conclusion, the nanotoxicity of amorphous 10SiO(2)-NP on submucosal cells is associated with inflammation, the release of ROS leading to apoptosis, and decreased cell survival. The nanotoxic effects of 10SiO(2)-NP can be decreased by fisetin and catalase treatment, implicating oxidative stress in this injury.