Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: A comparison with n-acetylcysteine

被引:35
作者
Ahmad, Akbar
Mondello, Stefania [2 ]
Di Paola, Rosanna [3 ]
Mazzon, Emanuela [3 ]
Esposito, Emanuela [3 ]
Catania, Maria Antonietta
Italiano, Domenico [3 ]
Mondello, Patrizia [3 ]
Aloisi, Carmela [3 ]
Cuzzocrea, Salvatore [1 ,3 ]
机构
[1] Univ Messina, Sch Med, Policlin Univ, Dept Clin & Expt Med & Pharmacol, I-98100 Messina, Italy
[2] Univ Messina, Dept Internal Med, I-98100 Messina, Italy
[3] IRCCS Ctr Neurolesi Bonino Pulejo, Messina, Italy
关键词
Apocynin; NADPH-oxidase; Contrast induced nephropathy; CHRONIC KIDNEY-DISEASE; OXYGEN-FREE-RADICALS; NITRIC-OXIDE; ACTIVATION; HYPOXIA; CELLS; ZYMOSAN; FAILURE; MEDIA; PATHOPHYSIOLOGY;
D O I
10.1016/j.ejphar.2011.10.041
中图分类号
R9 [药学];
学科分类号
100702 [药剂学];
摘要
The aim of this study was to investigate the effects of apocynin, a NADPH (nicotinamide adenine dinucleotide phosphate)-oxidase inhibitor, in diabetic rats with nephropathy induced by contrast medium (CIN). Diabetes was induced in male Wistar rats by a single dose of streptozotocin (60 mg/kg i.v.). Animals were then divided into the following groups: 1) control group (diabetic rats treated i.v. with saline solution): 2) iomeprol group (iomeprol at 10 ml/kg was injected i.v. 30 min after saline administration); 3) apocynin group (identical to the iomeprol group, except for pre-treatment with apocynin 5 mg/kg i.v., 30 min before iomeprol injection) and 4) N-acetylcysteine group (NAC) (same as iomeprol group, except for the treatment with NAC 20 mg/kg iv. 30 min before iomeprol injection). CIN in animals were assessed 24 h after administration of iomeprol. Apocynin significantly attenuates the impaired glomerular function, concentration of Na+, K+, alpha glutathione S-transferase levels in urine and neutrophil gelatinase-associated lipocalin levels in plasma caused by iomeprol. In kidney, immunohistochemical analysis of some inflammatory mediators, such as nitrotyrosine, poly-ADP-ribosyl polymerase, tumor necrosis factor-alpha, interleukin-1 beta as well as apoptosis (evaluated as terminal deoxynucleotidyltransferase-mediated UTP end labeling assay) revealed positive staining in tissue obtained from iomeprol group. These parameters were markedly reduced in animals treated with apocynin. Similarly, these parameters were also markedly modified by NAC pre-treatment. Here, we have shown that apocynin attenuates the degree of iomeprol-induced nephropathy in diabetic rats. (C) 2011 Elsevier B.V. All rights reserved.
引用
收藏
页码:397 / 406
页数:10
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