Dursun M, Sahin S, Besiroglu H, Otunctemur A, Ozbek E, Cakir S S, Cekmen M, Somay A
Bratisl Lek Listy. 2018;119(11):718-725. doi: 10.4149/BLL_2018_128.
Nephrotoxicity is a major complication of gentamicin (GEN), which is widely used in the treatment of severe Gram-negative infections. As we know, treatment with nebivolol has been shown to decrease renal fibrosis and glomerular injury as well as improve endothelial dysfunction. Therefore, we evaluated the potential protective effect of nebivolol (NBV) against GEN-induced nephrotoxicity in rats.
Twenty-four rats were randomly divided into four groups: control group (Group 1); rats intraperitoneally injected with GEN (100 mg/kg/day; Group 2); rats treated with GEN plus distilled water (Group 3); and rats treated with GEN plus NBV (10 mg/kg/day; Group 4). After 15 days, the rats were sacrificed, their kidneys taken, and blood analysis performed. Tubular necrosis and interstitial fibrosis scores were determined histopathologically in a part of kidneys; nitric oxide (NO), malondialdehyde (MDA), and reduced glutathione (GSH) levels were determined in other part of kidneys.
The GSH levels in renal tissue of only GEN-treated rats were significantly lower than those in control group, and administration of NBV to GEN-treated rats significantly increased the level of GSH. The group that was given GEN and NBV had significantly lower MDA and NO levels in kidney cortex tissue than that given GEN alone. Despite the presence of mild tubular degeneration, the rats treated with GEN+NBV showed a less severe tubular necrosis, and their glomeruli maintained a better morphology compared to GEN group.
NBV exerts antioxidant, anti-inflammatory and antifibrotic effects on GEN-induced kidney damage by reducing oxidative stress in rat model (Tab. 3, Fig. 2, Ref. 68).
肾毒性是庆大霉素(GEN)的主要并发症,庆大霉素广泛用于治疗严重革兰氏阴性菌感染。众所周知,奈必洛尔治疗已显示可减少肾纤维化和肾小球损伤,并改善内皮功能障碍。因此,我们评估了奈必洛尔(NBV)对大鼠GEN诱导的肾毒性的潜在保护作用。
24只大鼠随机分为四组:对照组(第1组);腹腔注射GEN的大鼠(100mg/kg/天;第2组);用GEN加蒸馏水治疗的大鼠(第3组);以及用GEN加NBV(10mg/kg/天;第4组)治疗的大鼠。15天后,处死大鼠,取出肾脏并进行血液分析。在部分肾脏中通过组织病理学确定肾小管坏死和间质纤维化评分;在另一部分肾脏中测定一氧化氮(NO)、丙二醛(MDA)和还原型谷胱甘肽(GSH)水平。
仅接受GEN治疗的大鼠肾组织中的GSH水平显著低于对照组,给接受GEN治疗的大鼠施用NBV可显著提高GSH水平。给予GEN和NBV的组肾皮质组织中的MDA和NO水平显著低于仅给予GEN的组。尽管存在轻度肾小管变性,但与GEN组相比,接受GEN+NBV治疗的大鼠肾小管坏死程度较轻,其肾小球形态保持较好。
在大鼠模型中,NBV通过降低氧化应激对GEN诱导的肾损伤发挥抗氧化、抗炎和抗纤维化作用(表3,图2,参考文献68)。