Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt.
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, 35516 Mansoura, Egypt; Faculty of Pharmacy, New Mansoura University, 7723730 New Mansoura, Egypt.
Life Sci. 2022 Aug 1;302:120646. doi: 10.1016/j.lfs.2022.120646. Epub 2022 May 17.
Acute kidney injury (AKI) is a clinical disorder with a serious impact on the quality of patients' lives. Considering its increased worldwide prevalence, investigating novel therapeutic approaches for the management of AKI has been inevitable. Lactoferrin (LF), a glycoprotein belonging to the transferrin family, is known to play an important role in regulating iron homeostasis. This study aimed to evaluate the renoprotective effect of LF (30, 100, and 300 mg/kg orally) against glycerol (GLY)-induced rhabdomyolysis (RM) in rats. RM was induced by a single intramuscular injection of GLY 50% (10 mL/kg) after 24-h water deprivation in male Sprague-Dawley rats. LF administration conferred significant dose-dependent renoprotective impact against GLY-induced RM as evidenced by the decreased renal/somatic index and the significant improvement in renal functions as confirmed by the significant increase in creatinine clearance, decrease in serum creatinine and blood urea nitrogen, and improvement in albuminuria and proteinuria. Redox homeostasis was significantly restored in a dose-dependent manner as well. Moreover, serum interleukin-1β (IL-1β) was significantly decreased with a parallel significant decrease in renal NOD-like receptor family pyrin domain containing 3 (NLRP3) and thioredoxin interacting protein (TXNIP), kidney injury molecule-1 (KIM-1), caspase-3 expression, nuclear factor kappa B (NF-κB), cluster of differentiation (CD68) expression, and a significant increase in renal nuclear factor erythroid 2-related factor 2 (NRF2) expression. Ultimately, LF administration was associated with a significant amelioration of GLY-induced renal necrotic and inflammatory alterations. In conclusion, the observed dose-dependent nephroprotective effect of LF can be attributed to its modulatory impact on inflammatory/apoptotic/oxidative signaling.
急性肾损伤 (AKI) 是一种对患者生活质量有严重影响的临床疾病。鉴于其在全球的患病率不断增加，研究 AKI 管理的新治疗方法已成为必然。乳铁蛋白 (LF) 是转铁蛋白家族的一种糖蛋白，已知在调节铁平衡方面发挥着重要作用。本研究旨在评估 LF（30、100 和 300mg/kg 口服）对甘油 (GLY) 诱导的大鼠横纹肌溶解症 (RM) 的肾保护作用。RM 通过在雄性 Sprague-Dawley 大鼠 24 小时断水后，单次肌内注射 GLY 50%（10 mL/kg）诱导。LF 给药对 GLY 诱导的 RM 具有显著的剂量依赖性肾保护作用，表现为肾/体指数降低，肾功能显著改善，肌酐清除率显著增加，血清肌酐和血尿素氮降低，白蛋白尿和蛋白尿改善。氧化还原平衡也呈剂量依赖性显著恢复。此外，血清白细胞介素-1β (IL-1β) 显著降低，肾 NOD 样受体家族吡啶结构域包含 3 (NLRP3) 和硫氧还蛋白相互作用蛋白 (TXNIP)、肾损伤分子-1 (KIM-1)、半胱天冬酶-3 表达、核因子 kappa B (NF-κB)、分化 (CD68) 表达平行显著降低，肾核因子红细胞 2 相关因子 2 (NRF2) 表达显著增加。最终，LF 给药与 GLY 诱导的肾坏死和炎症改变的显著改善相关。总之，LF 的观察到的剂量依赖性肾保护作用可归因于其对炎症/凋亡/氧化信号的调节作用。
