Effects of Chlorogenic Acid on Deoxynivalenol (DON)-Induced Ferroptosis in Porcine Alveolar Macrophages

Deoxynivalenol (DON) is a mycotoxin commonly found in food crops and animal feed worldwide. Its pronounced toxicity in pigs poses a serious risk to the swine industry and to human health. This study focused on two central features of ferroptosis—iron metabolism and lipid peroxidation—and examined how chlorogenic acid (CGA) affects DON-induced ferroptosis in porcine alveolar macrophages (PAMs) via cell-based assays and oxidative lipid metabolomics. These findings show that DON disrupts intracellular iron homeostasis by altering iron-handling proteins (upregulating TFR1 and DMT1 and downregulating FPN1), which may lead to iron overload. Concurrently, DON impairs the GPX4 antioxidant axis (downregulating GPX4, SLC3A2, SLC7A11, and GCLC) and increases ROS, and exposure led to a significant increase in numerous oxidized lipid metabolites, consistent with elevated lipid peroxidation, culminating in ferroptosis in PAMs. CGA mitigates these effects by restoring iron homeostasis and reestablishing GPX4 axis function, thereby reducing oxidative stress. Moreover, CGA suppresses lipid peroxidation pathways, notably linoleic acid oxidation metabolism. In conclusion, CGA protects PAMs and mitigates the proferroptotic effects of DON.