Lycopene Protects Deoxynivalenol-Induced Intestinal Barrier Dysfunction and NLRP3 Inflammasome Activation by Targeting the ERK Pathway

In agricultural production, Deoxynivalenol (DON) generally exists and contaminates wheat, corn, and other grains, causing intestinal damage and immunotoxicity. Lycopene (LYC), an antioxidant, anti-inflammatory carotenoid, is mainly found in red fruits such as tomatoes and has been investigated for its great medicinal advantages. This study aimed to investigate the protective effect of LYC against DON-induced enterotoxicity. Our findings demonstrated that incubation of IPEC-J2 cells with 0.5 μM DON for 24 h caused intestinal barrier impairment and oxidative stress induction, which subsequently led to increased secretion of pro-inflammatory factors (TNF-α, IL-1β, IL-18, and IL-6) and decreased secretion of the counterregulatory factor (IL-10). Furthermore, DON ultimately induced NLRP3 inflammasome activation through the stimulation of the MAPK/NF-κB pathway. It is worth mentioning that the above changes were reversed after adding 30 μg/mL of LYC to DON-exposed IPEC-J2 cells. In addition, further experiments confirmed that ERK activator (4-Methylbenzylidene camphor, 4-MBC) eliminated the positive effect of LYC on alleviating enterotoxicity induced by DON in IPEC-J2 cells. In addition, further experiments confirmed that 4-MBC eliminated the positive effect of LYC on alleviating enterotoxicity induced by DON. In general, our study certified that ERK is a therapeutic target for LYC protecting DON-induced intestinal barrier dysfunction and NLRP3 inflammasome activation.