Department of Nutrition and Food Hygiene, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
Department of Toxicology, Guangdong Provincial Key Laboratory of Tropical Disease Research, School of Public Health, Southern Medical University, Guangzhou 510515, China.
J Hazard Mater. 2021 May 5;409:124502. doi: 10.1016/j.jhazmat.2020.124502. Epub 2020 Nov 13.
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-α 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.
介孔硅纳米颗粒（MSNs）的生物安全性逐渐受到关注。然而，关于其对肠道的毒性及其机制的研究甚少。本研究对其一级结构进行了表征，并对其亚急性毒性进行了研究。在灌胃给予 MSNs 2 周后，MSNs 显著提高了血清碱性磷酸酶（ALP）、丙氨酸转氨酶（ALT）、天冬氨酸转氨酶（AST）和肿瘤坏死因子-α（TNF-α）水平，并导致脾脏和肠道中炎症细胞浸润。MSNs 诱导了小鼠的肠道氧化应激和结肠上皮细胞凋亡。MSN 处理后，肠上皮细胞出现线粒体嵴破裂和膜电位降低。此外，MSNs 增加了 ROS 和 NLRP3 水平，并抑制了自噬蛋白 LC3-II 和 Beclin1 的表达。MSNs 显著改变了小鼠的肠道菌群多样性，特别是有害细菌，导致肠道微生态失衡。同时，MSNs 影响了代谢物的表达，这些代谢物涉及多种代谢途径，包括嘧啶代谢、癌症中心碳代谢、蛋白质消化吸收、矿物质吸收、ABC 转运和嘌呤代谢。这些结果表明，介孔硅的亚急性毒性主要是由肠道损伤引起的。因此，我们的研究为 MSNs 在临床和食品工业中的安全剂量提供了更多证据。
