Abstract
Acute kidney injury (AKI) is a clinical syndrome with high morbidity and mortality worldwide, and there is currently no effective means to prevent it. Dioscin is naturally present in the dioscoreaceae plants and has antioxidant and anti-inflammatory effects. Here, we found that dioscin is protective against cisplatin-induced AKI. Pathological and ultrastructural observations revealed that dioscin reduced renal tissue lesions and mitochondrial damage. Furthermore, dioscin markedly suppressed reactive oxygen species and malondialdehyde levels in the kidneys of AKI rats and increased the contents of glutathione and catalase. In addition, dioscin dramatically reduced the number of apoptotic cells and the expression of pro-apoptotic proteins in rat kidneys and human renal tubular epithelial cells (HK2). Conversely, the protein levels of anti-ferroptosis including GPX4 and FSP1 in vivo and in vitro were significantly enhanced after dioscin treatment. Mechanistically, dioscin promotes the entry of Nrf2 into the nucleus and regulates the expression of downstream HO-1 to exert renal protection. However, the nephroprotective effect of dioscin was weakened after inhibiting Nrf2 in vitro and in vivo. In conclusion, dioscin exerts a reno-protective effect by decreasing renal oxidative injury, apoptosis and ferroptosis through the Nrf2/HO-1 signaling pathway, providing a new insight into AKI prevention.