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.

Macrophages participate in local and systemic inflammation induced by amorphous silica nanoparticles through intratracheal instillation

“…However, the SiNPs induced local and systemic inflammatory actions and therefore the macrophages may have been recruited and circulated by blood and lymph circulation. Although the acute toxicity of SiNPs had already been described, 17,24 this study reveals that the inflammation may be sustained for a longer period and that the macrophages play a pivotal role in local and systemic inflammation.…”

“…This study aimed to analyze the mechanisms of inflammation induced by SiNPs through the respiration pathway. Repeated dose toxicity studies were performed herein as most in vivo reports previously published have focused on acute toxicity 16,17 and do not provide an indication of the toxic effects in the longer term. The histopathology and ultrastructure variations of some and Il-1β; the group of lipopolysaccharide (LPS) used as positive control, and tubulin was used as the internal control.…”

“…Previous studies have shown that nanoparticles can penetrate organs following ingestion, injection, skin application, or inhalation through systemic circulation. 7,16,17 Herein, SiNPs may have been transported into other organs, but there was no obvious evidence of this having occurred. However, SiNPs in the lung may have induced the secretion of inflammatory factors, thus affecting systemic and other tissues' reactions.…”

“…Further, the intraperitoneal treatment of amorphous SiNPs probably induced inflammation and DNA damage in the lung, heart, liver, kidney, and brain. 17 Most of the studies were concerned with the acute toxicity.…”

Chronic Kidney Diseases and Nanoparticle Therapeutics

“…Amorphous silica (SiO2) is used in biopharmaceutical and industrial fields. SiNPs causes oxidative stress, inflammation, and DNA damage in several major organs [73]. The delivery of siRNA is made to find out liver and kidney functions [74,75].…”