title: Protective effect of apocynin, a NADPH-oxidase inhibitor, against contrast-induced nephropathy in the diabetic rats: a comparison with n-acetylcysteine.
abstract: 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 5mg/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 i.v. 30 min before iomeprol injection). CIN in animals were assessed 24h 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-α, interleukin-1β 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.
authors.affiliation: Department of Clinical and Experimental Medicine and Pharmacology, School of Medicine, Messina, Italy.
authors.forename: Akbar
authors.initials: A
authors.lastname: Ahmad
authors.forename: Stefania
authors.initials: S
authors.lastname: Mondello
authors.forename: Rosanna
authors.initials: R
authors.lastname: Di Paola
authors.forename: Emanuela
authors.initials: E
authors.lastname: Mazzon
authors.forename: Emanuela
authors.initials: E
authors.lastname: Esposito
authors.forename: Maria Antonietta
authors.initials: MA
authors.lastname: Catania
authors.forename: Domenico
authors.initials: D
authors.lastname: Italiano
authors.forename: Patrizia
authors.initials: P
authors.lastname: Mondello
authors.forename: Carmela
authors.initials: C
authors.lastname: Aloisi
authors.forename: Salvatore
authors.initials: S
authors.lastname: Cuzzocrea
mesh_terms: D000098:Acetophenones / Q000494:pharmacology*; D000111:Acetylcysteine / Q000494:pharmacology*; D000209:Acute-Phase Proteins / Q000652:urine; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003287:Contrast Media / Q000009:adverse effects*; D003596:Cytosine / Q000378:metabolism; D003928:Diabetic Nephropathies / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005982:Glutathione Transferase / Q000652:urine; D007479:Iopamidol / Q000031:analogs & derivatives / Q000494:pharmacology; D007527:Isoenzymes / Q000652:urine; D007678:Kidney Glomerulus / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D000071068:Lipocalin-2; D054834:Lipocalins / Q000652:urine; D008297:Male; D019255:NADPH Oxidases / Q000037:antagonists & inhibitors*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D011188:Potassium / Q000097:blood; D011518:Proto-Oncogene Proteins / Q000652:urine; D051381:Rats; D017208:Rats, Wistar; D012964:Sodium / Q000097:blood; D013997:Time Factors; D014443:Tyrosine / Q000031:analogs & derivatives / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000209:Acute-Phase Proteins; D003287:Contrast Media; D004791:Enzyme Inhibitors; D007527:Isoenzymes; C097278:Lcn2 protein, rat; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; C057937:iomeprol; C002744:3-nitrotyrosine; D014443:Tyrosine; D003596:Cytosine; D012964:Sodium; C056165:acetovanillone; D019255:NADPH Oxidases; D011065:Poly(ADP-ribose) Polymerases; D005982:Glutathione Transferase; C119995:glutathione S-transferase alpha; D007479:Iopamidol; D011188:Potassium; D000111:Acetylcysteine