Background: Acute kidney injury (AKI) poses a serious threat to patients' health, creating an urgent need for effective prevention and treatment strategies. Propofol, an anesthetic used in clinical practice, has demonstrated protective effects across several organs. This study aims to explore the effect of propofol on AKI and its underlying mechanism.

Methods: An AKI model was established by using lipopolysaccharide (LPS) injection. At 24 hours post-operation, renal function was evaluated through biochemical analyzers and hematoxylin-eosin staining. The level of oxidative stress was detected using a biochemical kit. Iron death-related proteins in kidney tissues were evaluated by Western blot (WB) analysis, and iron deposition was observed by Perls staining. The levels of inflammatory factors were detected by Enzyme-linked immunosorbent assay (ELISA) and immunohistochemistry. In vitro experiments were performed using human proximal tubular epithelial cells (HK-2). Cell viability was detected by Cell Counting Kit-8 assay, intracellular reactive oxygen species (ROS) was detected by flow cytometry, and the expression of ferroptosis-related proteins was determined by WB.

Results: In the in vivo experiments, propofol treatment significantly improved renal function (p < 0.05). The indicators related to oxidative stress and ferroptosis were downregulated (p < 0.05). The levels of inflammatory factors were reduced, and the activation of the inflammatory body was suppressed (p < 0.05). The in vitro experiments showed that propofol could significantly increase the cell viability of HK-2 (p < 0.05), reduce ROS production (p < 0.05), downregulate ferroptosis-related proteins levels (p < 0.05), and inflammatory responses (p < 0.05). Upon induction of ferroptosis with Erastin, the protective effect of propofol was attenuated (p < 0.05).

Conclusions: Propofol has a significant protective effect on AKI, mainly through inhibiting ferroptosis and inflammatory responses in renal tubular epithelial cells. This research provides a strong theoretical basis and experimental foundation for the clinical application of propofol in the prevention and treatment of AKI.