Low dose of arsenic exacerbates toxicity to mice and IPEC-J2 cells exposed with deoxynivalenol: Aryl hydrocarbon receptor and autophagy might be novel therapeutic targets
2022
Liu, Shuiping | Kang, Weili | Mao, Xinru | Du, Heng | Ge, Lei | Hou, Lili | Yuan, Xin | Wang, Mengmeng | Chen, Xingxiang | Liu, Yunhuan | Huang, Kehe
Deoxynivalenol (DON) and arsenic (As) are widespread environmental contaminants, which are frequently found in human and animal food products. The intestine is a common target of As and DON when they are digested. Numerous studies mainly evaluate the individual effects whereas their combined toxicity has rarely been elucidated. Hence, this study was to assess the effect of low dose of NaAsO₂ on DON-induced intestinal damage and explore the underling mechanism in mice and IPEC-J2 cells. The results showed that low dose of NaAsO₂ exacerbated DON-induced intestinal impairment by increasing intestinal permeability and decreasing the abundance of tight junction proteins (ZO-1, Occludin, Claudin-1). Further, low dose of NaAsO₂ enhanced the AhR signaling pathway and autophagy-related mRNA/protein expressions induced by DON. Interestingly, FICZ, an AhR activator, instead of CH223191, an AhR inhibitor, could alleviate toxicity of the low dose of NaAsO₂ in the mice and IPEC-J2 cells. Compared to the WT IPEC-J2 cells, the intestinal barrier damage was more serious in LC3B⁻/⁻ IPEC-J2 cells induced by low dose of NaAsO₂ combination with DON. Collectively, our study demonstrated that low dose of NaAsO₂ exacerbated DON-induced intestinal barrier impairment in vivo and in vitro. The present study also demonstrated that activation of AhR-mediated autophagy might be a self-protection mechanism. Hence, AhR and autophagy might be novel therapeutic targets to prevent or alleviate NaAsO₂ combined with DON-induced intestinal barrier impairment.
Afficher plus [+] Moins [-]Mots clés AGROVOC
Informations bibliographiques
Cette notice bibliographique a été fournie par National Agricultural Library
Découvrez la collection de ce fournisseur de données dans AGRIS