2-((3-(chloromethyl) benzoyl) oxy) benzoic acid suppresses NF-κB expression in the kidneys and lungs of LPS-Induced BALB/C mice.

Sepsis, a life-threatening systemic inflammatory condition, is a leading cause of mortality worldwide. Its pathophysiology involves the activation of nuclear factor kappa beta (NF-κB), which promotes the release of proinflammatory cytokines. Acetylsalicylic acid (ASA), a widely used nonsteroidal anti-inflammatory drug, inhibits NF-κB but poses risks of peptic ulcer disease and nephrotoxicity. This study evaluates the efficacy of 2-((3-(chloromethyl)benzoyl)oxy)benzoic acid (3-CH₂Cl), a novel salicylate derivative, in reducing NF-κB expression in the kidneys and lungs of lipopolysaccharide (LPS)-induced septic BALB/C mice. Mice were divided into four groups: untreated, LPS only, LPS + ASA (60 mg/kg BW), and LPS + 3-CH₂Cl (60 mg/kg BW). NF-κB expression was assessed via immunohistochemistry. LPS significantly increased NF-κB expression in both renal and pulmonary tissues compared to controls (P < 0.0001). While ASA treatment reduced NF-κB levels (P < 0.0001), 3-CH₂Cl demonstrated superior suppression in the renal cortex, renal medulla, and alveolar regions (P < 0.05). In addition, 3-CH₂Cl alleviated hypothermia in septic mice, comparable to ASA. Given its enhanced anti-inflammatory efficacy and reduced gastrointestinal risk, 3-CH₂Cl presents a promising alternative to ASA for sepsis-related inflammation management. Further studies are warranted to explore its clinical applications.