Quercetin alleviates zearalenone-induced apoptosis and necroptosis of porcine renal epithelial cells by inhibiting CaSR/CaMKII signaling pathway

Abstract

Zearalenone (ZEA) is a mycotoxin that is highly contaminated in feed and can cause severe toxic effects on the kidneys and other organs of animals. Quercetin (QUE) is a plant-derived flavonoid with a variety of detoxification properties, but the mechanism by which QUE detoxifies the toxic effects induced by ZEA has not yet been fully elucidated. We treated porcine kidney cells (PK15) with 80 μM ZEA and/or 30 μM QUE. The results showed that ROS and MDA levels were increased, antioxidant system levels were down-regulated, anti-apoptotic factor expression levels were decreased, and apoptotic and necroptosis-related factors were up-regulated after ZAE exposure. In addition, the results of Ca2+ staining, mitochondrial membrane potential, and mitochondrial dynamics-related indicators showed that ZEA induced Ca2+ overload in PK15 cells and increased mitochondrial Ca2+ uptake (MCU expression increased). The accumulated ROS and free Ca2+ further aggravate mitochondrial damage and eventually lead to mitochondrial pathway apoptosis and necroptosis. Nevertheless, QUE targets CaSR to inhibit the CaSR/CaMKII pathway and regulate calcium homeostasis, thereby alleviating apoptosis and necroptosis mediated by mitochondrial dynamic disorder and dysfunction. The present study demonstrated the mechanism by which ZEA induces apoptosis and necroptosis in PK15 and the protective role of QUE in this process.