Journal
JOURNAL OF HAZARDOUS MATERIALS
Volume 409, Issue -, Pages -Publisher
ELSEVIER
DOI: 10.1016/j.jhazmat.2020.124502
Keywords
Mesoporous silica nanoparticles; Oral exposure; Subacute Toxicity; Intestinal flora; Metabolomics
Categories
Funding
- Guangdong Key RD Program [2019B020210002]
- National Natural Science Foundation of China [81973013]
- Natural Science Foundation of Guangdong Province [2018030310301, 2020A1515010594]
- Guangdong Regular Institutions of Higher Learning Characteristic Innovation Projects [2018KTSCX030]
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This study investigated the subacute toxicity of mesoporous silica nanoparticles (MSNs) in mice and found that they induced intestinal oxidative stress, apoptosis in colonic epithelial cells, mitochondrial damage, and alterations in intestinal flora composition. Additionally, MSNs affected the expression of metabolites involved in various metabolic pathways. These results suggest that the subacute toxicity of MSNs is mainly due to intestinal damage.
The biological safety of mesoporous silica nanoparticles (MSNs) has gradually attracted attention. However, few studies of their toxicity to the intestine and mechanism are available. In this study, their primary structures were characterized, and their subacute toxicity to mice was investigated. After 2 weeks of intragastric administration of MSNs, they significantly enhanced serum ALP, ALT, AST and TNF-alpha levels and caused infiltration of inflammatory cells in the spleen and intestines. MSNs induced intestinal oxidative stress and colonic epithelial cell apoptosis in mice. Intestinal epithelial cells exhibited mitochondrial ridge rupture and membrane potential decrease after MSN treatment. Additionally, MSNs increased ROS and NLRP3 levels and inhibited expression of the autophagy proteins LC3-II and Beclin1. MSNs significantly changed the intestinal flora diversity in mice, especially for harmful bacteria, leading to intestinal microecology imbalance. Meanwhile, MSNs influenced the expression of metabolites, which were involved in a range of metabolic pathways, including pyrimidine metabolism, central carbon metabolism in cancer, protein digestion and absorption, mineral absorption, ABC transport and purine metabolism. These results indicated that the subacute toxicity of mesoporous silicon was mainly caused by intestinal damage. Thus, our research provides additional evidence about the safe dosage of MSNs in the clinical and food industries.
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