Department of Urology, Okmeydani Training and Research Hospital, Istanbul, Turkey.
Ren Fail. 2013;35(3):403-10. doi: 10.3109/0886022X.2012.761040. Epub 2013 Jan 24.
Nephrotoxicity is a major complication of gentamicin (GEN). We aimed to evaluate the potential protective effect of montelukast (MK) against GEN-induced nephrotoxicity in rats. Thirty-two rats were randomly divided into four groups, each consisting of eight animals as follows: (1) the rats were control; (2) intraperitoneally injected with GEN 14 consecutive days (100 mg/kg/day); (3) treated with GEN plus distilled water via nasogastric gavage for 14 days; and (4) treated with GEN plus MK (10 mg/kg/day) for 14 days. After 15 days, rats were killed and their kidneys were taken and blood analysis was performed. Twenty-four hours urine collections were obtained in standard metabolic cages a day before the rats were killed. Tubular necrosis and interstitial fibrosis scoring were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in the other part of kidneys. Statistical analyses were made by the chi-square test and analysis of variance. Serum urea and creatinine levels were significantly higher in rats treated with GEN alone, than the rats in control and GEN + MK groups.The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of MK to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and MK had significantly lower MDA and NO levels in kidney cortex tissue than those that was given GEN alone. In rats treated with GEN + MK, despite the presence of mild tubular degeneration and tubular necrosis are less severe, and glomeruli maintained a better morphology when compared with GEN group. We can say that MK prevents kidney damage with antioxidant effect, independently of NO.
肾毒性是庆大霉素(GEN)的主要并发症。我们旨在评估孟鲁司特(MK)对大鼠 GEN 诱导的肾毒性的潜在保护作用。32 只大鼠随机分为四组,每组 8 只,如下:(1)对照组;(2)连续 14 天腹腔注射 GEN(100mg/kg/天);(3)连续 14 天经鼻胃管给予 GEN 加蒸馏水;(4)连续 14 天经鼻胃管给予 GEN 加 MK(10mg/kg/天)。15 天后处死大鼠,取肾,进行血液分析。在处死大鼠前一天,在标准代谢笼中收集 24 小时尿液。一部分肾脏进行组织病理学检查,确定肾小管坏死和间质纤维化评分;另一部分肾脏测定一氧化氮(NO)、丙二醛(MDA)和还原型谷胱甘肽(GSH)水平。采用卡方检验和方差分析进行统计学分析。与对照组和 GEN+MK 组相比,单独用 GEN 处理的大鼠血清尿素和肌酐水平显著升高。只有 GEN 处理的大鼠肾组织中 GSH 水平明显低于对照组,而给予 MK 可显著增加 GEN 处理大鼠的 GSH 水平。与单独给予 GEN 的大鼠相比,给予 GEN 和 MK 的大鼠肾皮质组织中 MDA 和 NO 水平明显降低。在给予 GEN+MK 的大鼠中,尽管存在轻度的肾小管变性和肾小管坏死,但程度较轻,与 GEN 组相比,肾小球形态保持较好。我们可以说,MK 通过抗氧化作用防止肾损伤,与 NO 无关。