Renoprotective Effects of Montelukast in Sepsis-Induced AKI: Targeting the NF-κB Pathway

Background Sepsis-associated acute kidney injury (SA-AKI) is a common complication of sepsis and is associated with increased mortality among critically ill patients. Inflammatory activation, particularly via nuclear factor kappa B (NF-κB) signaling, plays a central role in the pathogenesis of acute kidney injury. Cecal ligation and puncture (CLP) is a well-established experimental model used to induce sepsis-associated renal injury in rodents. Montelukast is a cysteinyl leukotriene receptor antagonist with reported anti-inflammatory and antioxidant properties. It has been shown to modulate key pathogenic pathways implicated in acute kidney injury, including NF-κB signaling, oxidative stress, and inflammatory responses. However, its role in SA-AKI and the involvement of NF-κB-mediated pathways remain insufficiently explored. Aim This study aimed to investigate the potential renoprotective effects of montelukast against sepsis-induced acute kidney injury in a murine CLP model. Methods Forty male Swiss Albino mice were randomly allocated into four groups: sham, CLP, vehicle, and CLP + Montelukast. Montelukast (20 mg/kg) was administrated via intraperitoneal injection one hour before CLP induction. Renal function, inflammatory and oxidative stress markers, apoptotic parameters, and NF-κB p65 gene and protein expression were assessed using histological hematoxylin and eosin (H&E) staining, immunohistochemical (IHC) staining, quantitative reverse transcription polymerase chain reaction (qRT-PCR), and Enzyme-Linked Immunosorbent Assay (ELISA). Results The findings highlight that Montelukast significantly attenuated CLP-induced renal dysfunction as evidenced by reductions in serum blood urea nitrogen (BUN), creatinine (Cr), and kidney injury molecule (KIM) levels compared with the CLP group. In addition, renal levels of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), F2-isoprostane, and caspase-3 were markedly decreased (P