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持续口服纳米氧化铁会扰乱肠道-肝脏轴。

Sustained oral intake of nano-iron oxide perturbs the gut-liver axis.

机构信息

CAS Key Laboratory for Biomedical Effects of Nanomaterials and Nanosafety & CAS Center for Excellence in Nanoscience, National Center for Nanoscience and Technology of China, Beijing 100190, PR China; University of Chinese Academy of Sciences, Beijing 100049, PR China.

Zhengzhou University, Zhengzhou 450001, PR China.

出版信息

NanoImpact. 2023 Apr;30:100464. doi: 10.1016/j.impact.2023.100464. Epub 2023 Apr 15.

DOI:10.1016/j.impact.2023.100464
PMID:37068656
Abstract

Nanomaterial have shown excellent properties in the food industry. Although iron oxides are often considered safe and widely used as food additives, the toxicity of nano‑iron oxide remains unclear. Here we established a subchronic exposure mouse model by gavage, tested the biodistribution of nano‑iron oxide, and explored the mechanism of liver injury caused by it through disturbance of the gut-liver axis. Oral intake of nano‑iron oxide will likely disrupt the small intestinal epithelial barrier, induce hepatic lipid metabolism disorders through the gut-liver axis, and cause hepatic damage accompanied with hepatic iron deposition. Nano‑iron oxide mainly caused hepatic lipid metabolism disorder by perturbing glycerophospholipid metabolism and the sphingolipid metabolism pathways, with the total abundance of phosphatidylcholine (PC) and phosphatidylethanolamine (PE) tending to decrease while that of triglyceride tended to increase, in a time- and dose-dependent manner. The imbalanced lipid homeostasis could cause damage via membrane disruption, lipid accumulation, and lipotoxicity. This data provides information about the subchronic toxicity of nano‑iron oxide, highlights the importance of gut-liver axis in the hepatotoxicity.

摘要

纳米材料在食品工业中表现出优异的性能。尽管氧化铁通常被认为是安全的,并广泛用作食品添加剂,但纳米氧化铁的毒性仍不清楚。在这里,我们通过灌胃建立了一个亚慢性暴露的小鼠模型,测试了纳米氧化铁的生物分布,并通过干扰肠-肝轴探索了它引起肝损伤的机制。纳米氧化铁的口服摄入可能会破坏小肠上皮屏障,通过肠-肝轴诱导肝脂质代谢紊乱,并导致伴有肝铁沉积的肝损伤。纳米氧化铁主要通过扰乱甘油磷脂代谢和鞘脂代谢途径引起肝脂质代谢紊乱,随着时间和剂量的增加,总胆碱(PC)和磷脂酰乙醇胺(PE)的含量趋于减少,而甘油三酯的含量趋于增加。脂质代谢失衡会通过破坏膜、脂质积累和脂毒性造成损伤。该数据提供了纳米氧化铁亚慢性毒性的信息,强调了肠-肝轴在肝毒性中的重要性。

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