Quercetin protects chicken mesenchymal stem cells from DEHP- induced toxicity by modulating the ROS/Wnt/β-catenin pathway

Di-2-ethylhexyl phthalate (DEHP), a ubiquitous plasticizer, induces systemic organ damage primarily via oxidative stress. Quercetin (Que), a flavonoid abundant in vegetables, possesses anti-inflammatory, anti-allergic, and antioxidant properties. Whether Que protects avian gizzard tissue against DEHP insult through modulation of the ROS/Wnt/β-catenin axis remains unclear. Network toxicology indicated that DEHP could trigger chicken gastritis via oxidative stress, apoptosis, and autophagy. In vitro and in vivo experiments corroborated these predictions: DEHP exposure markedly elevated oxidative stress, suppressed Wnt/β-catenin signaling at both protein and mRNA levels, down-regulated autophagy-related genes, and up-regulated pro-apoptotic markers. Concomitant Que treatment reversed these alterations. Importantly, the protective effect of Que was abolished when either the oxidative-stress activator sanguinarine or the pathway inhibitor Wnt-C59 was added. Collectively, Que modulates the Wnt/β-catenin pathway in a ROS-dependent manner, thereby inhibiting DEHP-induced apoptosis and restoring autophagy in chicken gizzard mesenchymal stem cells. These findings provide new insights into the toxicology of DEHP in poultry and wild birds, and support the development of plant-derived formulations to prevent or mitigate phthalate poisoning in livestock.