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

Background Sepsis-associated acute kidney injury is ubiquitous among patients with critical conditions and contributes to high mortality rates. SA-AKI was experimentally elicited in murine models via cecal ligation and puncture. Aims This study aimed to determine the possible protective effects of montelukast on sepsis-induced acute kidney injury in a mouse sepsis model. Methods Albino male Swiss mice (n = 40) were allocated into four distinct groups: (i) normal group, (ii) CLP group, (iii) vehicle group, and (iv) Cecal Ligation and Puncture + Montelukast group (20 mg/kg one hour before Cecal Ligation and Puncture). Blood and tissue biochemical/routine indicators, renal function, Sepsis-associated acute kidney injury -related pathophysiological processes, and nuclear factor kappa B (NF-κB) p65 gene expression in septic mice were assessed by histological hematoxylin and eosin (H&E) staining, immunohistochemical (IHC) staining, quantitative reverse transcription polymerase chain reaction, and Enzyme-Linked Immunosorbent Assay. Results The findings highlight that Montelukast reversed CLP-induced increases in serum blood urea nitrogen, creatinine (Cr), and kidney injury molecule levels. It also significantly inhibited elevated concentrations of interleukin (IL)-1β, tumor necrosis factor alpha (TNF-α), F2-isoprostane, and caspase-3 in renal tissues. Additionally, NF-κB protein levels were notably lower in the CLP+ montelukast group than in Cecal Ligation and Puncture group P<0.001. In addition, montelukast significantly mitigated extensive tubular damage in the murine sepsis group p<0.001. Conclusion These findings indicate that montelukast may serve as a promising therapeutic agent for sepsis-induced AKI.