New Strategies for the Prevention and Control of Foodborne Mycotoxins: Glycyrrhizic Acid Enhances Antioxidant Capacity and Modulates the ROS/NF-κB/NLRP3 Pathway to Treat Zearalenone-Induced Lung Injury in Chickens

Zearalenone is an estrogen-like mycotoxin produced by <i>Fusarium fungi</i>. Growing evidence shows that ZEA causes multisystem damage via oxidative stress. Glycyrrhizic acid (GA), from <i>Glycyrrhiza glabra</i>, has anti-inflammatory/antioxidant properties. The mechanisms of GA and ZEA in chicken pulmonary oxidative stress and inflammation remain elusive. Therefore, we established zearalenone-exposed chicken lung and CP-II cells models. ZEA exposure triggers an inflammatory cascade via the ROS-NF-κB axis, activating NLRP3 inflammasomes and promoting the release of proinflammatory factors. It also increased the apoptosis-related factors and fibrosis-related factors. GA treatment reduced oxidative stress, inflammation, and apoptosis, while suppressing fibrosis. This study reveals that GA reverses lung tissue injury by suppressing oxidative stress, inflammation, and the apoptosis-necrosis network through regulating the NF-κB/NLRP3 signaling axis by scavenging ZEA-induced reactive oxygen species (ROS). These results elucidate the antioxidant mechanism of GA and provide insights into the toxicology of ZEA.