Maldonado Perla D, Barrera Diana, Medina-Campos Omar N, Hernández-Pando Rogelio, Ibarra-Rubio María E, Pedraza-Chaverrí José
Department of Biology, Faculty of Chemistry, Universidad Nacional Autónoma de México, Ciudad Universitaria, 04510 D.F., México, Mexico.
Life Sci. 2003 Oct 3;73(20):2543-56. doi: 10.1016/s0024-3205(03)00609-x.
Gentamicin (GM) is an antibiotic whose clinical use is limited by its nephrotoxicity. Experimental evidences suggest a role of reactive oxygen species in GM-induced nephrotoxicity. Therefore, we investigated if aged garlic extract (AGE), an antioxidant, has a protective role in this experimental model. Four groups of male Wistar rats were studied: 1) Control (CT), injected subcutaneously (s.c.) and intraperitoneally (i.p.) with saline, 2) GM, treated s.c. with GM (70 mg/kg/12 hours/4 days), 3) AGE, treated i.p with AGE (1.2 mL/kg/12 hours/6 days), and 4) GM + AGE treated with GM and AGE. The treatment with AGE started two days before the first dose of GM (GM + AGE group) or saline (AGE group). Animals were sacrificed on day 5, and blood, urine, and kidneys were obtained. Nephrotoxicity was made evident by: 1) the increase in blood urea nitrogen and plasma creatinine, 2) the decrease in plasma glutathione peroxidase (GPx) activity and the urinary increase in N-acetyl-beta-D-glucosaminidase activity and total protein, and 3) necrosis of proximal tubular cells. These alterations were prevented or ameliorated by AGE treatment. Furthermore, AGE prevented the GM-induced increase in the renal levels of oxidative stress markers: nitrotyrosine and protein carbonyl groups and the decrease in manganese superoxide dismutase (Mn-SOD), GPx, and glutathione reductase (GR) activities. The protective effect of AGE was associated with the decrease in the oxidative stress and the preservation of Mn-SOD, GPx, and GR activities in renal cortex. These data suggest that AGE may be a useful agent for the prevention of GM-nephrotoxicity.
庆大霉素(GM)是一种抗生素,其临床应用因肾毒性而受到限制。实验证据表明活性氧在GM诱导的肾毒性中起作用。因此,我们研究了抗氧化剂老年大蒜提取物(AGE)在该实验模型中是否具有保护作用。研究了四组雄性Wistar大鼠:1)对照组(CT),皮下(s.c.)和腹腔内(i.p.)注射生理盐水;2)GM组,皮下注射GM(70mg/kg/12小时/4天);3)AGE组,腹腔注射AGE(1.2mL/kg/12小时/6天);4)GM + AGE组,同时接受GM和AGE治疗。AGE治疗在首次给予GM(GM + AGE组)或生理盐水(AGE组)前两天开始。在第5天处死动物,获取血液、尿液和肾脏。肾毒性表现为:1)血尿素氮和血浆肌酐升高;2)血浆谷胱甘肽过氧化物酶(GPx)活性降低,尿N-乙酰-β-D-氨基葡萄糖苷酶活性和总蛋白增加;3)近端肾小管细胞坏死。AGE治疗可预防或改善这些改变。此外,AGE可预防GM诱导的肾氧化应激标志物水平升高:硝基酪氨酸和蛋白质羰基基团,以及锰超氧化物歧化酶(Mn-SOD)、GPx和谷胱甘肽还原酶(GR)活性降低。AGE的保护作用与氧化应激降低以及肾皮质中Mn-SOD、GPx和GR活性的保留有关。这些数据表明AGE可能是预防GM肾毒性的有用药物。