Foe Kuncoro, Karel Philipus, Ervina Martha, Tjahjono Yudy, Wijaya Hendy, Dewi Bernadette Dian Novita, Putri Claritta Angelina Wiyanto, Partana Fransiskus Regis, Angelina Michelle, Dewi Sianty, Esar Senny Yesery, Hadinugroho Wuryanto, Wihadmadyatami Hevi
Departement of Cellular Pharmacology, Faculty of Pharmacy, Widya Mandala Catholic University, Surabaya, East Java, Indonesia.
Departement of Pharmacology, Faculty of Medicine, Widya Mandala Catholic University, Surabaya, East Java, Indonesia.
J Adv Pharm Technol Res. 2025 Jul-Sep;16(3):163-168. doi: 10.4103/JAPTR.JAPTR_61_25. Epub 2025 Aug 9.
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-CHCl), 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-CHCl (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 ( < 0.0001). While ASA treatment reduced NF-κB levels ( < 0.0001), 3-CHCl demonstrated superior suppression in the renal cortex, renal medulla, and alveolar regions ( < 0.05). In addition, 3-CHCl alleviated hypothermia in septic mice, comparable to ASA. Given its enhanced anti-inflammatory efficacy and reduced gastrointestinal risk, 3-CHCl presents a promising alternative to ASA for sepsis-related inflammation management. Further studies are warranted to explore its clinical applications.
脓毒症是一种危及生命的全身性炎症性疾病，是全球范围内主要的死亡原因。其病理生理学涉及核因子κB（NF-κB）的激活，NF-κB会促进促炎细胞因子的释放。乙酰水杨酸（ASA）是一种广泛使用的非甾体抗炎药，可抑制NF-κB，但存在消化性溃疡疾病和肾毒性风险。本研究评估了新型水杨酸盐衍生物2-((3-(氯甲基)苯甲酰基)氧基)苯甲酸（3-CHCl）在降低脂多糖（LPS）诱导的脓毒症BALB/C小鼠肾脏和肺中NF-κB表达方面的疗效。将小鼠分为四组：未治疗组、仅LPS组、LPS + ASA（60 mg/kg体重）组和LPS + 3-CHCl（60 mg/kg体重）组。通过免疫组织化学评估NF-κB表达。与对照组相比，LPS显著增加了肾脏和肺组织中NF-κB的表达（<0.0001）。虽然ASA治疗降低了NF-κB水平（<0.0001），但3-CHCl在肾皮质、肾髓质和肺泡区域表现出更好的抑制作用（<0.05）。此外，3-CHCl减轻了脓毒症小鼠的体温过低，与ASA相当。鉴于其增强的抗炎疗效和降低的胃肠道风险，3-CHCl是ASA用于脓毒症相关炎症管理的一个有前景的替代药物。有必要进行进一步研究以探索其临床应用。
