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

Abstract

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.

Ferroptosis and Acute Kidney Injury (AKI): Molecular Mechanisms and Therapeutic Potentials

“…Zhou et al recently reported that polydatin enabled to attenuate the cell ferroptosis in cisplatin-induced AKI via regulating system Xc−/GSH/GPX4 pathway and inhibiting iron metabolism disorders ( Zhou et al, 2022 ). Deng et al found Se/Albumin nanoparticles could alleviate cisplatin-induced AKI by inhibiting ferroptosis with a decrease of superoxide dismutase, and up-regulation of GSH and GPX4 ( Deng et al, 2022 ).…”

Nanodrugs alleviate acute kidney injury: Manipulate RONS at kidney

“…Among these, selenium, phosphorus, and carbon are essential elements for human physiology [ 183 , 184 ]. Currently, nanoparticles based on these elements have been adopted for AKI treatment, with excellent therapeutic effects and extremely low side effects [ [185] , [186] , [187] , [188] , [189] ]. For example, Rosenkranz et al adopted selenium-doped carbon quantum dots (SeCQDs) for AKI antioxidant therapy ( Fig.…”

Broadening horizons: the multifaceted functions of ferroptosis in kidney diseases

“…Ferrostatin-1 or polydatin could inhibit ferroptosis in CI-AKI mice by regulating the GSH/GPX4 signaling pathway [114]. In a CI-AKI mouse model, selenium nanoparticle administration effectively inhibited ferroptosis by decreasing lipid peroxide accumulation and increasing GPX4 activity [115]. In addition, Hu et al found that the activation of the vitamin D receptor could inhibit ferroptosis by upregulating GPX4 expression, thereby improving renal function and alleviating kidney injury in CI-AKI mice [116].…”