Endotoxin promotes adverse effects of amorphous silica nanoparticles on lung epithelial cells in vitro

Amorphous silica engineered nanoparticles (ENP) are used for drug delivery and food additive under current regulations. Although the adverse effects of amorphous silica ENP may be negligible, contamination by bacterium products may enhance the toxic potential of these so-called safe products. Lipopolysaccharide (LPS), an endotoxin component generated by gram-negative bacteria, is a potential contaminant of amorphous silica ENP due to its ubiquitous presence in the environment. The combined effects of amorphous silica ENP and LPS are therefore of particular concern. In this study, A549 cells were exposed to amorphous silica ENP in combination with LPS for comparison with the cells treated with ENP. Measurements of MTT assay and lactate dehydrogenase (LDH) activity indicated that the toxicity of amorphous silica ENP was low but co-treatment of the cells with LPS significantly enhanced this toxicity. Decreased cell viability and increased LDH activity release occurred earlier and at lower concentration levels in co-treated cells. Co-treatment of LPS with amorphous silica ENP might also enhance the increase in oxidative stress produced by amorphous silica ENP. However, there were no detectable changes in nitric oxide generation and 8-hydroxy-2-deoxy guanosine formation in the cells treated with either ENP or ENP plus LPS, indicating low effect on oxidative DNA damage. These results showed that LPS may enhance the oxidative stress induced by amorphous silica ENP to initiate cytotoxicity of these engineered nanoparticles.