Oridonin Protects Mice Against Cadmium-induced Kidney Injury by Inhibiting Ferroptosis via SIRT1 Regulation

Kidney injury is a clinical condition characterized by a rapid decline in renal function, associated with high morbidity and mortality. This study aimed to investigate the protective effects and mechanism of oridonin against cadmium-induced kidney injury in mice. A mouse model of cadmium-induced kidney injury was established by cadmium administration. Inflammatory cytokines were tested by ELISA. Protein expression was measured by western blot analysis. Oridonin treatment reduced cadmium-induced serum creatinine and blood urea nitrogen (BUN), kidney myeloperoxidase (MPO) activity, and TNF-α and IL-1β production. Oridonin also alleviated pathological changes in the kidney caused by cadmium. Furthermore, cadmium-induced hypoxia-inducible factor-1α (HIF-1α), NLRP3 inflammasome and NF-κB activation were inhibited by oridonin. Oridonin also suppressed cadmium-induced ferroptosis. In addition, oridonin upregulated SIRT1 expression and the protective effects of oridonin on cadmium-induced inflammation and ferroptosis were abolished by SIRT1 inhibitor. In conclusion, oridonin attenuates cadmium-induced kidney injury by activating SIRT1, which in turn suppresses inflammation and ferroptosis.