Kuncoro Foe, Philipus Karel, Martha Ervina, Yudy Tjahjono, Hendy Wijaya, Bernadette Dian Novita Dewi, Claritta Angelina Wiyanto Putri, Fransiskus Regis Partana, Michelle Angelina, Sianty Dewi, Senny Yesery Esar, Wuryanto Hadinugroho, Hevi Wihadmadyatami, Caroline
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-CH 2 Cl), 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-CH 2 Cl (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-CH 2 Cl demonstrated superior suppression in the renal cortex, renal medulla, and alveolar regions (P < 0.05). In addition, 3-CH 2 Cl alleviated hypothermia in septic mice, comparable to ASA. Given its enhanced anti-inflammatory efficacy and reduced gastrointestinal risk, 3-CH 2 Cl presents a promising alternative to ASA for sepsis-related inflammation management. Further studies are warranted to explore its clinical applications. © 2025 Journal of Advanced Pharmaceutical Technology & Research.
Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, East Java, Surabaya, Indonesia; Departement of Pharmacology, Faculty of Medicine, Widya Mandala Catholic University, East Java, Surabaya, Indonesia; Department of Anatomy, Faculty of Veterinary Medicine, Gadjah Mada University, Karangmalang, Yogyakarta, Indonesia
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