Kadkhodaee Mehri, Khastar Hossein, Faghihi Mahdieh, Ghaznavi Rana, Zahmatkesh Maryam
Department of Physiology, Faculty of Medicine, Tehran University of Medical Sciences, 14174 Tehran, Iran.
Exp Physiol. 2005 Jul;90(4):571-6. doi: 10.1113/expphysiol.2004.029728. Epub 2005 Mar 15.
Gentamicin (GM) is an effective antibiotic against severe gram-negative infections. However it can produce nephrotoxicity in human. Reactive oxygen species (ROS) have been proposed as the causative factors of the renal side effects the drug. This study was performed to investigate the protective role of antioxidant vitamins against GM-mediated nephropathy in an in situ model of isolated rat kidney. Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: group 1 (Control) was perfused with Tyrode solution; group 2 (GM), 200 microg ml(-1) GM was added to the perfusate; group 3 (GM + Vit C), as group 2 with vitamin C added to the drinking water for 3 days (200 mg l(-1)) and to the perfusate (100 mg l(-1)); group 4 (GM + Vit E), as group 2 with vitamin E (100 mg (100 g body weight)(-1), i.m.) injected 12 h before the start of the experiment; group 5 (GM + Vit C + Vit E) as group 2 with vitamin E and C co-administered (concentrations and conditions as in groups 3 and 4). To compare the groups, urinary lactate dehydrogenase (LDH), N-acetyle-beta-D-glucosaminidase (NAG) and alkaline phosphatase (ALP) activities, inulin clearance (glomerular filtration rate, GFR) and renal tissue glutathione (GSH) content were measured. GM caused a significant nephrotoxicity demonstrated by an increase in urinary LDH, NAG and ALP activities. Reduction in GSH content and a marked decrease in GFR were observed compared to controls. Vitamin C inhibited the GM-induced increase in urinary enzyme activities but did not show a significant effect on the GSH content or GFR. Vitamin E prevented the GM-induced reduction in GSH level without a significant improvement in GFR. Co-administration of vitamins C and E significantly prevented the GM-induced nephrotoxicity demonstrating by preservation of GFR and GSH levels and prevention of increase in urinary enzyme activities. We conclude that co-administration of moderate doses of vitamins C and E has beneficial effects on renal preservation in GM-induced nephrotoxicity.
庆大霉素（GM）是一种治疗严重革兰氏阴性菌感染的有效抗生素。然而，它会对人体产生肾毒性。活性氧（ROS）被认为是该药物肾脏副作用的致病因素。本研究旨在探讨抗氧化维生素在大鼠离体肾脏原位模型中对GM介导的肾病的保护作用。将雄性Sprague-Dawley大鼠随机分为以下几组，每组7只：第1组（对照组）用台氏液灌注；第2组（GM组），在灌注液中加入200μg/ml GM；第3组（GM + 维生素C组），与第2组相同，但在饮水中添加维生素C 3天（200mg/l），并在灌注液中添加（100mg/l）；第4组（GM + 维生素E组），与第2组相同，但在实验开始前12小时肌肉注射维生素E（100mg/（100g体重））；第5组（GM + 维生素C + 维生素E组），与第2组相同，但同时给予维生素E和C（浓度和条件同第3组和第4组）。为比较各组情况，检测了尿乳酸脱氢酶（LDH）、N-乙酰-β-D-氨基葡萄糖苷酶（NAG）和碱性磷酸酶（ALP）活性、菊粉清除率（肾小球滤过率，GFR）以及肾组织谷胱甘肽（GSH）含量。GM导致显著的肾毒性，表现为尿LDH、NAG和ALP活性增加。与对照组相比，GSH含量降低，GFR显著下降。维生素C抑制了GM诱导的尿酶活性增加，但对GSH含量或GFR没有显著影响。维生素E防止了GM诱导的GSH水平降低，但GFR没有显著改善。维生素C和E联合使用显著预防了GM诱导的肾毒性，表现为GFR和GSH水平得以维持，尿酶活性增加得到预防。我们得出结论，中等剂量的维生素C和E联合使用对GM诱导的肾毒性中的肾脏保护具有有益作用。
