Xu Tongxiao, Huangfu Bingxin, Chen Yanan, Ban Qiushi, Zhang Feng, Huang Kunlun, Liang Zhihong, He Xiaoyun
Key Laboratory of Precision Nutrition and Food Quality, Key Laboratory of Functional Dairy, Ministry of Education, College of Food Science and Nutritional Engineering, China Agricultural University, Beijing 100083, China.
College of Veterinary Medicine, China Agricultural University, Beijing 100094, China.
J Hazard Mater. 2025 Aug 15;494:138737. doi: 10.1016/j.jhazmat.2025.138737. Epub 2025 May 26.
Zearalenone (ZEA) is a fungal toxin that is commonly found in grains and feeds. It has been demonstrated that this toxin can induce oxidative stress and inflammation, which can result in liver damage in humans and animals. Exosomes have the capacity to carry active substances, and when these particles are released into the blood, they can transport these substances to other cells, thereby affecting the health of the body. However, the specific mechanism of action remains to be elucidated. This study was conducted with the objective of investigating the exosome-mediated liver injury of ZEA in rats and its possible mechanism. Firstly, the systemic toxic effects of ZEA exposure were clarified at the animal level. It was found that ZEA induced an elevation in the levels of exosome in the serum of rats. Subsequent analysis determined that the main source of exosomes were the liver. Secondly, transcriptomics was used to screen out the microRNAs (miRNA) let-7d-3p in exosomes, which may mediate the liver damage induced by ZEA. Furthermore the mechanism of exosomes and miRNA let-7d-3p involved in the hepatotoxicity induced by ZEA was explored. Compared with database, we clarified that ZEA caused liver damage through the let-7d-3p/Arid5a signaling pathway. This study revealed the role of exosomes on intercellular communication in ZEA hepatotoxicity, providing a new perspective for ZEA toxicity and its prevention and control.
玉米赤霉烯酮（ZEA）是一种常见于谷物和饲料中的真菌毒素。已经证明，这种毒素可诱导氧化应激和炎症，进而导致人和动物的肝脏损伤。外泌体能够携带活性物质，当这些颗粒释放到血液中时，它们可以将这些物质运输到其他细胞，从而影响身体的健康。然而，其具体作用机制仍有待阐明。本研究旨在探讨ZEA通过外泌体介导的大鼠肝损伤及其可能机制。首先，在动物水平上阐明了ZEA暴露的全身毒性作用。发现ZEA可导致大鼠血清中外泌体水平升高。随后的分析确定外泌体的主要来源是肝脏。其次，利用转录组学筛选出外泌体中的微小RNA（miRNA）let-7d-3p，其可能介导ZEA诱导的肝损伤。此外，还探讨了外泌体和miRNA let-7d-3p参与ZEA诱导的肝毒性的机制。与数据库对比后，我们明确ZEA通过let-7d-3p/Arid5a信号通路导致肝损伤。本研究揭示了外泌体在ZEA肝毒性细胞间通讯中的作用，为ZEA毒性及其防治提供了新的视角。
