4′-Hydroxydehydrokawain Mitigate the Cytotoxicity of Citrinin in Porcine Intestinal Epithelial Cells

Citrinin (CTN) is a mycotoxin that adversely affects livestock by contaminating stored grains, leading to significant health and economic impacts. This study investigates the toxicological effects of CTN on porcine small intestinal epithelial cells (IPEC-J2) and explores potential mitigation strategies using natural products and chemical inhibitors. Our study demonstrates that CTN induces cytotoxicity through the TGF-β signaling pathway, triggering apoptosis and G2/M phase cell cycle arrest. We examined cell viability, cell cycle progression, and gene expression changes in IPEC-J2 cells treated with CTN, 4'-Hydroxydehydrokawain (4-HDK), and LY-364947, a TGF-β receptor inhibitor. LY-364947 treatment confirmed that CTN-induced toxicity is mediated through TGF-β signaling. Although 4-HDK alleviated CTN-induced cytotoxicity by improving cell viability and reducing apoptosis, its direct involvement in TGF-β inhibition remains unclear. These results suggest that CTN disrupts intestinal epithelial cell homeostasis via TGF-β activation, whereas 4-HDK may exert protective effects through an alternative mechanism. Our study provides novel insights into CTN-induced toxicity mechanisms and highlights the therapeutic potential of 4-HDK as a mitigator of mycotoxin-induced cellular damage.