Quercetin alleviates Deoxynivalenol-induced myocardial fibrosis in chicken by regulating MCU-mediated mitochondrial calcium overload.

Deoxynivalenol (DON), a trichothecene mycotoxin commonly found in contaminated cereals, poses a major threat to animals and human health. While DON-induced damage to the intestines, liver, and kidneys in chickens is well-documented, its cardiac toxicity remains insufficiently characterized. Quercetin (QUE), a plant-derived flavonoid with antioxidant and cytoprotective properties, has been shown to protect against cardiac damage. However, it is unclear whether QUE has a protective effect against DON-induced cardiac damage in chicken. Therefore, this study combined an in vivo chicken model of DON-exposure (10 mg/kg) with in vitro experiments using chicken embryo primary cardiomyocytes, supplemented with QUE treatment (4 mg/kg), to investigate the potential mechanisms of DON-induced cardiac injury. This study revealed that QUE significantly ameliorated DON-induced myocardial fibrosis (by 12.36 %), apoptosis (by 41.26 %), and oxidative stress (ROS levels decreased by 8.07 %). Further studies validated that QUE attenuated mitochondrial dysfunction by suppressing mitochondrial calcium uniporter (MCU)-induced mitochondrial calcium overload. MCU knockdown mimicked the protective phenotype of QUE, confirming MCU as a key therapeutic target in DON-mediated cardiac mitochondrial dysfunction. In summary, these findings demonstrate that QUE mitigates DON cardiotoxicity by targeting MCU-dependent mitochondrial calcium dysregulation, highlighting its therapeutic potential in mitigating DON-induced cardiac damage. Future studies should further explore the upstream regulatory pathways of MCU and evaluate the translational potential of QUE in other animal models or clinical settings.