Aloe-emodin mitigates cisplatin-induced acute kidney injury by Nrf2-mediated ferroptosis regulation.

Acute kidney injury (AKI) is a common clinical critical illness, with currently limited treatment options available. Cisplatin (CDDP), a first-line drug for cancer chemotherapy, a significant contributor to nephrotoxicity, which severely restricts its clinical application. Therefore, there is an urgent need for pharmacological interventions to alleviate cisplatin (CDDP)-induced acute kidney injury (CI-AKI). Aloe-emodin (AE), as a novel ferroptosis inhibitor, shows great potential in mitigating cisplatin-induced acute kidney injury. This study aims to explore the effect and mechanism of aloe-emodin on cisplatin-induced acute kidney injury. By establishing in vitro and in vivo models, we evaluated indicators related to renal function, oxidative stress, ferroptosis, and the nuclear factor erythroid 2-related factor 2 (Nrf2) pathway using techniques such as biochemical analysis, immunofluorescence, and Western blotting. The results indicated that AE significantly improves renal function indices, reduces levels of oxidative stress products, inhibits alterations in ferroptosis marker molecules, and alleviates renal pathological damage. Mechanistically, AE activates the Nrf2 pathway and upregulates the expression of its downstream antioxidant and anti-ferroptosis genes. Inhibition of the Nrf2 pathway significantly diminishes the protective effects of AE. This study suggests that AE mitigates CI-AKI by activating the Nrf2 pathway and inhibiting ferroptosis, thus providing new insights for clinical prevention and treatment.