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:

• amorphous silica nanoparticles
• organ toxicity
• oxidative stress
• inflammation
• DNA damage

Acknowledgments

This work was supported by funds of the CMHS grant (31M215), and UAEU Program for Advanced Research (31M189) and center-based interdisciplinary (31R052) grants.

The authors wish to thank Saeed Tariq, Department of Anatomy, CMHS, UAEU, for his help in the electromagnetic analysis.

The authors wish to thank Professor Gerald Blunden (University of Portsmouth, UK) for critically reading the manuscript.

Disclosure

The authors report no conflicts of interest in this work.