Abdelrahman R S
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Mansoura University, Mansoura, Egypt.
Hum Exp Toxicol. 2018 Jan;37(1):27-37. doi: 10.1177/0960327116689716. Epub 2017 Jan 24.
Gentamicin (GNT) is an aminoglycoside antibiotic used for treatment of serious infections, and the nephrotoxic adverse effect is one of the main therapeutic limitations. This study aimed to investigate the possible protective effect of apocynin (APO) on nephrotoxicity induced by GNT in rats. Twenty-four rats were allocated into three groups: control, GNT (100 mg/kg, intraperitoneally (i.p.)), and GNT plus APO (10 mg/kg, i.p.). All rats were killed at the end of the experiment, and then the blood, urine, and kidneys samples were taken. GNT-induced nephrotoxicity was manifested by a significant ( p < 0.05) increase in the weight of kidney, 24-h urine volume, renal somatic index (RSI), protein in urine, serum lactate dehydrogenase (LDH), creatinine (Cr), blood urea nitrogen (BUN), renal Fas ligand (CD95), nitric oxide (NO), and malondialdehyde (MDA). Furthermore, a significant reduction in body weight, creatinine clearance (CCr), serum albumin, renal superoxide dismutase (SOD), and glutathione activities were detected when compared with the control rats. APO ameliorated the nephrotoxic effect and oxidative damage caused by GNT by improving tissue morphology and significantly decreasing 24-h urine volume, RSI, serum Cr, LDH and BUN, protein in urine, and renal content of MDA, CD95, and NO. Additionally, APO caused a significant elevation in renal SOD activity and CCr when compared with the GNT group. These results confirm that APO by its anti-inflammatory, antiapoptotic, and antioxidant effects can ameliorate GNT-induced nephrotoxicity.
庆大霉素(GNT)是一种用于治疗严重感染的氨基糖苷类抗生素,其肾毒性不良反应是主要治疗限制之一。本研究旨在探讨阿扑辛(APO)对GNT诱导的大鼠肾毒性可能的保护作用。将24只大鼠分为三组:对照组、GNT组(100mg/kg,腹腔注射(i.p.))和GNT加APO组(10mg/kg,i.p.)。实验结束时处死所有大鼠,然后采集血液、尿液和肾脏样本。GNT诱导的肾毒性表现为肾脏重量、24小时尿量、肾体指数(RSI)、尿蛋白、血清乳酸脱氢酶(LDH)、肌酐(Cr)、血尿素氮(BUN)、肾Fas配体(CD95)、一氧化氮(NO)和丙二醛(MDA)显著(p<0.05)增加。此外,与对照大鼠相比,体重、肌酐清除率(CCr)、血清白蛋白、肾超氧化物歧化酶(SOD)和谷胱甘肽活性显著降低。APO通过改善组织形态并显著降低24小时尿量、RSI、血清Cr、LDH和BUN、尿蛋白以及肾MDA、CD95和NO含量,减轻了GNT引起的肾毒性作用和氧化损伤。此外,与GNT组相比,APO使肾SOD活性和CCr显著升高。这些结果证实,APO通过其抗炎、抗凋亡和抗氧化作用可减轻GNT诱导的肾毒性。