Tanshinone IIA protects intestinal epithelial cells from deoxynivalenol-induced pyroptosis

Abstract

Deoxynivalenol (DON) is the most common mycotoxin in food and feed, which can cause undesirable effects, including diarrhea, emesis, weight loss, and growth delay in livestock. Intestinal epithelial cells were the main target of DON, which can cause oxidative stress and inflammatory injury. Tanshinone IIA (Tan IIA) is fat-soluble diterpene quinone, which is the most abundant active ingredient in salvia miltiorrhiza plant with antioxidant and anti-inflammatory characteristics. However, it is not clear whether Tan IIA can protect against or inhibit intestinal oxidative stress and inflammatory injury under DON exposure. This study aimed to explore the protective effect of Tan IIA on DON-induced toxicity in porcine jejunum epithelial cells (IPEC-J2). Cells were exposed to 0, 0.5, 1.0, 2.0 µM DON and/or 45 µg/mL TAN ⅡA to detect oxidative stress indicators. inflammatory cytokines, NF-κB expression, NLRP3 inflammasome and pyroptosis-related factors. In this study, DON exposure caused IPEC-J2 cells oxidative stress by elevating ROS and 8-OHdG content, inhibited GSH-Px activity. Furthermore, DON increased pro-inflammatory factor (TNF-α, IL-1β, IL-18 and IL-6) expression and decreased the anti-inflammatory factor (IL-10) expression, causing inflammatory response via triggering NF-κB pathway. Interestingly, above changes were alleviated after Tan IIA treatment. In addition, Tan IIA relieved DON-induced pyroptosis by suppressing the expression of pyroptosis-related factors (NLRP3, Caspase-1, GSDMD, IL-1β, and IL-18). In general, our data suggested that Tan IIA can ameliorate DON-induced intestinal epithelial cells injury associated with suppressing the pyroptosis signaling pathway. Our findings pointed that Tan IIA could be used as the potential therapeutic drugs on DON-induced enterotoxicity.

Keywords: Deoxynivalenol; Inflammatory; Intestinal toxicity; Pyroptosis; Tanshinone IIA.