Lycopene Alleviates Deoxynivalenol-Induced Porcine Intestinal Epithelial Barrier Injury by Inhibiting PGAM5-Mediated...

Deoxynivalenol (DON), a mycotoxin produced by Fusarium species, is a major and unavoidable environmental contaminant that poses serious risks to intestinal health. Lycopene (LYC), a natural carotenoid with potent antioxidant properties, has been reported to exert protective effects against oxidative stress. Phosphoglycerate mutase family member 5 (PGAM5) acts as a key signaling hub to control mitochondrial dynamics and mitophagy. This study aimed to elucidate the potential role of LYC in DON-induced intestinal damage and clarify the contribution of PGAM5. We established intestinal porcine epithelial cell models to explore the effects of DON and LYC on intestinal barrier integrity, mitochondrial function, mitophagy, and ferroptosis through assessments of cell viability, oxidative stress, iron accumulation, and autophagic activity. Mechanistic insights were validated using RNA sequencing, molecular docking, Western blotting, and immunofluorescence analyses. PGAM5 expression was modulated via plasmids and small interfering RNA. Our results demonstrated that DON disrupted barrier integrity, reduced cell motility, and induced cytoskeletal disorganization, accompanied by excessive mitophagy, lipid peroxidation, and ferrous iron accumulation, ultimately leading to ferroptosis. Notably, LYC alleviated DON-induced intestinal damage by inhibiting mitophagy and ferroptosis. Importantly, PGAM5 overexpression abolished the protective effects of LYC, indicating that PGAM5-mediated mitophagy-dependent ferroptosis plays a critical role in DON-induced intestinal damage. These findings suggest that LYC may serve as a potential therapeutic strategy for treating mycotoxin-induced intestinal disorders.