Exosome encapsulated miRNA let-7d-3p mediated Zearalenone-induced hepatotoxicity with Arid5a/STAT3 signaling pathway.

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.