Yildiz Ilknur Esen, Mercantepe Tolga, Bahceci Ilkay, Arpa Medeni, Batcik Sule, Yildiz Yasin, Tumkaya Levent
Department of Infectious Diseases and Clinical Microbiology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
Department of Histology and Embryology, Faculty of Medicine, Recep Tayyip Erdogan University, 53100 Rize, Turkey.
Life (Basel). 2024 Dec 24;15(1):2. doi: 10.3390/life15010002.
Sepsis, a life-threatening condition characterized by dysregulated host responses to infection, often leads to multi-organ dysfunction, including kidney injury. Kidney damage in sepsis can have severe consequences and is associated with high mortality rates. This study aimed to investigate the potential therapeutic effects of fosfomycin (FOS), a broad-spectrum antibiotic with immunomodulatory properties, on kidney damage induced by cecal ligation and puncture (CLP)-induced sepsis in a rodent model. In total, 24 rats were randomly divided into three groups. Group 1 ( = 8), the healthy control group (C), received a single dose of 0.9% NaCl (saline) solution via an intraperitoneal (i.p.) route. To group 2 ( = 8), the CLP group, CLP-induced sepsis was applied without medication, and a single dose of 0.9% NaCl (saline) solution was applied i.p. before induction. To group 3 ( = 8), the CLP + FOS (500 mg/kg) group, a single dose of 500 mg/kg FOS was administered i.p. before sepsis induction. The effects of fosfomycin on kidney function, histopathological changes, inflammatory markers, oxidative stress, and apoptosis were assessed. In the fosfomycin-treated group, the histological analysis results demonstrated reduction in kidney tissue damage and inflammation. Additionally, fosfomycin attenuated the upregulation of pro-inflammatory cytokines and reduced oxidative stress markers in kidney tissue. Furthermore, fosfomycin treatment was associated with a decrease in apoptotic cell death in the kidney. These findings suggest that fosfomycin may have a protective effect on kidney damage caused by CLP-induced sepsis. The potential mechanisms underlying this protection include the modulation of inflammation, reduction of oxidative stress, and inhibition of apoptosis.
脓毒症是一种因宿主对感染的反应失调而危及生命的病症,常导致多器官功能障碍,包括肾损伤。脓毒症中的肾损伤可产生严重后果,并与高死亡率相关。本研究旨在探讨磷霉素(FOS)这一具有免疫调节特性的广谱抗生素,对啮齿动物模型中盲肠结扎穿刺(CLP)诱导的脓毒症所致肾损伤的潜在治疗作用。总共24只大鼠被随机分为三组。第1组(n = 8)为健康对照组(C),通过腹腔内(i.p.)途径接受单剂量的0.9%氯化钠(生理盐水)溶液。第2组(n = 8)为CLP组,施加CLP诱导的脓毒症但不给予药物治疗,并在诱导前经腹腔内给予单剂量的0.9%氯化钠(生理盐水)溶液。第3组(n = 8)为CLP + FOS(500 mg/kg)组,在脓毒症诱导前经腹腔内给予单剂量500 mg/kg的FOS。评估了磷霉素对肾功能、组织病理学变化、炎症标志物、氧化应激和细胞凋亡的影响。在磷霉素治疗组中,组织学分析结果显示肾组织损伤和炎症减轻。此外,磷霉素减弱了促炎细胞因子的上调,并降低了肾组织中的氧化应激标志物。此外,磷霉素治疗与肾组织中凋亡性细胞死亡的减少有关。这些发现表明,磷霉素可能对CLP诱导的脓毒症所致肾损伤具有保护作用。这种保护作用的潜在机制包括炎症调节、氧化应激减轻和细胞凋亡抑制。