Se/Albumin Nanoparticles for Inhibition of Ferroptosis in Tubular Epithelial Cells during Acute Kidney Injury

Cisplatin (DDP) is a widely used chemotherapeutic agent that plays an unsubstitutable role in treating various tumors. However, it is crucial to identify solutions and alternatives for DDP-mediated renal injury. This acute kidney injury (AKI) is characterized by the occurrence of ferroptosis, which is defined as an iron-catalyzed regulatory necrosis mediated by excessive lipid peroxidation. To solve this problem, we concentrate on the potential function of nanoparticles to devise a new technique to prevent DDP-induced kidney injury. Selenium nanoparticles (Se NPs) containing the trace element, selenium, have been shown to exhibit strong oxidation resistance. However, the ability of Se NPs to treat DDP-induced kidney injury remains largely unexplored. Here, we elaborate the role of our self-developed Se/Albumin nanoparticles (Se/Albumin NPs, SA NPs) in alleviating DDP-induced acute kidney damage using a murine model. Mice with acute kidney injury (AKI) had significantly impaired renal function and reduced body weight. Hematoxylin-eosin staining (H&E) and periodic acid-Schiff (PAS) staining, which was carried out to determine the extent of the morphological changes in renal tubules, revealed severe interstitial edema. Further studies revealed an increase in malonaldehyde (MDA), a decrease in superoxide dismutase (SOD), and reduced glutathione (GSH) and glutathione peroxidase (GPx) levels in the renal tubule tissues and cells under an electron microscope, thereby indicating pro-apoptotic changes. Moreover, the levels of ferroptosis-related proteins glutathione peroxidase 4 (GPX4) andferroportin1 (FPN1) decreased while those of transferrin and ACSL4 increased. Our study reveals that SA NPs are more potent at ameliorating these damages than Se NPs. In all, the results suggest that the SA NPs reduce DDP-induced AKI by inhibiting ferroptosis, indicating the potential therapeutic role of SA NPs in acute renal damage.