Dl-3-n-Butylphthalide Inhibits Ferroptosis and Attenuates Sepsis-Associated Acute Kidney Injury by Activating the Nrf2/HO-1 Pathway.

Abstract

BACKGROUND: This study aimed to investigate the protective effects of Dl-3-n-butylphthalide (NBP) on sepsis-associated acute kidney injury (SA-AKI) and its underlying mechanisms. METHODS: A total of 32 mice were randomly divided into 4 groups (n = 8 per group): the control group (control group), lipopolysaccharide treatment group (LPS group), Dl-3-n-butylphthalide group (LPS + NBP group), and ferrostatin-1 group (LPS + Fer-1 group). Renal function was assessed by measuring serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Oxidative stress markers, including malondialdehyde (MDA), superoxide dis-mutase (SOD), total antioxidant capacity (T-AOC), and glutathione (GSH), were quantified in renal tissues. Histopathological evaluation of renal injury was performed using hematoxylin and eosin (HE) staining. The protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4) were analyzed using immunohistochemistry and western blot. RESULTS: Compared with the control group, the LPS group exhibited significantly higher levels of SCr and BUN, decreased renal tissue levels of SOD, T-AOC, and GSH, as well as increased MDA levels and renal injury scores (p < 0.05). Furthermore, the LPS group exhibited significant downregulation of Nrf2, HO-1, GPX4, and SLC7A11 protein expression (p < 0.05). Compared with the LPS group, drug intervention significantly reversed the above-mentioned changes in both the LPS + NBP and LPS + Fer-1 groups (p < 0.05). CONCLUSIONS: NBP can attenuate SA-AKI by activating the Nrf2/HO-1 pathway.