Inhibition of ADAM17: A New Therapeutic Strategy to Alleviate Zearalenone Toxin-Induced Liver Injury by Endoplasmic Reticulum Stress and Inflammation.

Zearalenone (ZEA) is a mycotoxin that heavily contaminates feed and its raw materials, entering the body through dietary intake. Although it has been reported that ZEA causes liver damage, its toxic mechanisms are unclear. In this study, we first confirmed that ZEA induces liver injury in mice, triggering endoplasmic reticulum stress (ERS) and inflammation in vivo. Second, in vitro, we demonstrated that ZEA also causes ERS and inflammation in BRL 3A cells, with ERS playing a promoting role in ZEA-induced inflammation. Finally, we confirmed that ERS promotes ADAM17 expression in BRL 3A cells, and ADAM17 plays a facilitating role in ZEA-induced inflammation. In summary, these results indicate that ERS promotes ZEA-induced inflammation by upregulating ADAM17 expression. ADAM17 is a key target in ZEA-induced liver damage, and inhibition of ADAM17 represents a novel approach for treating liver damage. Furthermore, this study provides a new strategy for discovering effective therapeutic drugs.