Deoxynivalenol (DON) is widely distributed and chemically stable, posing a serious health risk. The kidney, as the primary metabolic organ, is a major target of DON toxicity, yet its mechanism remains unresolved. Using C57BL/6 mice and TCMK-1 cells, we established DON-induced injury models and observed activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, Caspase-1 activation, and cleavage of gasdermin D (GSDMD) to its N-terminal fragment (GSDMD-N). GSDMD-N translocated to the plasma membrane, formed pores, and promoted release of inflammatory mediators, culminating in pyroptosis. Treatment with the antioxidant N-acetyl-l-cysteine (NAC) significantly reduced intracellular reactive oxygen species (ROS) and suppressed pyroptosis-associated markers (P < 0.05), implicating oxidative stress as a key upstream driver. Collectively, these data indicate that DON induces renal tubular epithelial cell injury via the ROS/NLRP3/GSDMD-N pathway.
Wang et al. (Fri,) studied this question.