Rutin attenuates zearalenone-induced ferroptosis of endometrial stromal cells in piglets through the p53 signaling pathway.

Zearalenone (ZEA) is an environmentally widespread mycotoxin capable of posing a serious threat to food safety and public health, and porcine endometrial stromal cells (ESCs) are particularly sensitive to the toxic effects of ZEA. We hypothesized that Rutin, a flavonoid antioxidant, could significantly alleviate ZEA-induced ferroptosis through the p53 signaling pathway. In this study, we used porcine ESCs as a research model. When porcine ESCs were co-cultured with the addition of Rutin and ZEA following p53 gene silencing via siRNA transfection, Rutin significantly mitigated ZEA-induced mitochondrial damage, oxidative stress, and Fe content through the p53 pathway. Additionally Rutin lowered the expression of p53, ALOX12, and ACSL4 while significantly improving cytokinesis, antioxidant enzyme activity, and SLC7A11, GPX4, Nrf2, FTH1, thereby inhibiting cellular ferroptosis. These findings suggested a novel programmed death mechanism for alleviating the cytotoxic effects of ZEA, involving the knockdown of p53.