Curcumin Can Inhibit Zearalenone-Induced Ferroptosis in Porcine Intestinal Epithelial Cells via the p53/SLC7A11/GPX4 Pathway.

Zearalenone (ZEA) is a widely distributed estrogenic mycotoxin that can disrupt intestinal barrier integrity by inducing ferroptosis, thereby posing serious risks to animal health. Curcumin (CUR), as a natural polyphenolic compound with multi-target regulatory properties, has attracted increasing attention for its antioxidative and cytoprotective effects; however, its role in ZEA-induced ferroptosis remains poorly understood. In this study, the protective effects of curcumin (CUR) were evaluated in IPEC-J2 cells by co-treating the cells with zearalenone (ZEA) at its LC₅₀ (75.23 μM) and curcumin (5 or 15 μM) for 24 h. CCK-8 assays showed that CUR significantly (p < 0.05) and highly significantly (p < 0.01) improved cell viability in the 5 μM and 15 μM groups, respectively, compared with ZEA alone. CUR co-treatment significantly (p < 0.01) restored glutathione (GSH) levels, and markedly (p < 0.01) reduced Fe²⁺ accumulation, reactive oxygen species (ROS) production, malondialdehyde (MDA) content, and lipid peroxidation (LPO). Transmission electron microscopy revealed pronounced mitochondrial cristae loss and membrane collapse in ZEA-treated cells, which were visibly alleviated by CUR. At the molecular level, ZEA downregulated GPX4 and SLC7A11 and upregulated ACSL4, FTH1, and p53 (all p < 0.01), whereas these changes were significantly reversed (p < 0.05 or p < 0.01) by CUR. In conclusion, CUR exerts cytoprotective effects against ZEA-induced ferroptosis, likely via modulation of the p53/SLC7A11/GPX4 signaling pathway.