Nouripour Sadaf, Mehri Soghra, Aminifard Tahereh, Hosseini Arezoo, Khajavi Rad Abolfazl, Jafarian Amirhossein, Hosseinzadeh Hossein
Department of Pharmacodynamics and Toxicology, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran.
Pharmaceutical Research Center, Pharmaceutical Technology Institute, Mashhad University of Medical Sciences, Mashhad, Iran.
Iran J Basic Med Sci. 2024;27(8):1033-1039. doi: 10.22038/IJBMS.2024.74864.16252.
Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats.
Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins.
A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-α protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities.
Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI.
横纹肌溶解症是一种潜在的危及生命的疾病,当肌红蛋白从受损的肌肉细胞中释放出来时就会发生,进而导致急性肾损伤(AKI)。本研究检测了α硫辛酸(ALA)这种以其抗氧化和抗炎特性而闻名的有机硫化合物,对大鼠横纹肌溶解症诱导的急性肾损伤的潜在影响。
本研究纳入六组大鼠,每组六只(n = 6):对照组、横纹肌溶解症组、用不同剂量ALA(5、10和20 mg/kg)治疗的横纹肌溶解症组以及单独使用ALA(20 mg/kg)组。在实验第一天通过肌肉注射甘油诱导横纹肌溶解症,而ALA连续四天腹腔注射给药。评估肾功能参数、氧化应激标志物以及肾脏的组织学变化。进行蛋白质免疫印迹分析以测量中性粒细胞明胶酶相关脂质运载蛋白(NGAL)和肿瘤坏死因子-α(TNF-α)蛋白的水平。
在注射甘油的大鼠中观察到血清尿素、肌酐、肾丙二醛、NGAl和TNF-α蛋白水平显著升高。此外,谷胱甘肽水平显著降低。与横纹肌溶解症组相比,ALA治疗可恢复肾脏组织学和生化异常。
结果表明,横纹肌溶解症诱导的急性肾损伤与氧化应激和炎症增加有关。ALA治疗改善了大鼠肾脏组织学异常并降低了氧化应激标志物。因此,ALA可能对横纹肌溶解症诱导的急性肾损伤具有潜在的保护作用。