Oxidative stress, inflammation, and DNA damage in multiple organs of mice acutely exposed to amorphous silica nanoparticles

Abstract

The use of amorphous silica (SiO2) in biopharmaceutical and industrial fields can lead to human exposure by injection, skin penetration, ingestion, or inhalation. However, the in vivo acute toxicity of amorphous SiO2 nanoparticles (SiNPs) on multiple organs and the mechanisms underlying these effects are not well understood. Presently, we investigated the acute (24 hours) effects of intraperitoneally administered 50 nm SiNPs (0.25 mg/kg) on systemic toxicity, oxidative stress, inflammation, and DNA damage in the lung, heart, liver, kidney, and brain of mice. Lipid peroxidation was significantly increased by SiNPs in the lung, liver, kidney, and brain, but was not changed in the heart. Similarly, superoxide dismutase and catalase activities were significantly affected by SiNPs in all organs studied. While the concentration of tumor necrosis factor α was insignificantly increased in the liver and brain, its increase was statistically significant in the lung, heart, and kidney. SiNPs induced a significant elevation in pulmonary and renal interleukin 6 and interleukin-1 beta in the lung, liver, and brain. Moreover, SiNPs caused a significant increase in DNA damage, assessed by comet assay, in all the organs studied. SiNPs caused leukocytosis and increased the plasma activities of lactate dehydrogenase, creatine kinase, alanine aminotranferase, and aspartate aminotransferase. These results indicate that acute systemic exposure to SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs, and highlight the need for thorough evaluation of SiNPs before they can be safely used in human beings.

Keywords: DNA damage; amorphous silica nanoparticles; inflammation; organ toxicity; oxidative stress.

Figure 1

Electron micrograph of suspension of amorphous silica nanoparticles.

Figure 2

Circulating leukocyte numbers (A) and plasma activities of LDH (B) and CK (C) 24 hours after the administration of amorphous SiNPs (0.25 mg/kg) in mice (n=7–8). Abbreviations: LDH, lactate dehydrogenase; CK, creatine kinase; SiNPs, silica nanoparticles.

Figure 3

ALT (A) and AST (B) levels 24 hours after the administration of amorphous SiNPs (0.25 mg/kg) in mice (n=8). Abbreviations: ALT, alanine aminotransferase; AST, aspartate aminotransferase; SiNPs, silica nanoparticles.

Figure 4

Effect of SiNPs on DNA migration in various organs. Notes: DNA migration in the lung (A), heart (B), liver (C), kidney (D), and brain (E) tissues 24 hours after the administration of amorphous SiNPs (0.25 mg/kg) in mice. Data are mean ± SEM (n=5). Images illustrate the quantification of the DNA migration by the comet assay under alkaline conditions in the lung (F), heart (G), liver (H), kidney (I), and brain (J) tissues. The magnification in F–J is 20×. Abbreviations: SiNPs, silica nanoparticles; SEM, standard error of the mean.

Figure 4

Effect of SiNPs on DNA migration in various organs. Notes: DNA migration in the lung (A), heart (B), liver (C), kidney (D), and brain (E) tissues 24 hours after the administration of amorphous SiNPs (0.25 mg/kg) in mice. Data are mean ± SEM (n=5). Images illustrate the quantification of the DNA migration by the comet assay under alkaline conditions in the lung (F), heart (G), liver (H), kidney (I), and brain (J) tissues. The magnification in F–J is 20×. Abbreviations: SiNPs, silica nanoparticles; SEM, standard error of the mean.