Protective role of aminoguanidine on gentamicin-induced acute renal failure in rats

The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may prot...

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Bibliographic Details
Published in:Acta histochemica 2006-01, Vol.108 (5), p.365-371
Main Authors: Polat, Alaadin, Parlakpinar, Hakan, Tasdemir, Seda, Colak, Cemil, Vardi, Nigar, Ucar, Muharrem, Emre, Memet Hanifi, Acet, Ahmet
Format: Article
Language:English
Subjects:
Acute Kidney Injury - chemically induced
Acute Kidney Injury - pathology
Aminoguanidine
Animals
Female
Gentamicin
Gentamicins - pharmacology
Guanidines - pharmacology
Rat
Rats
Rats, Wistar
Reactive oxygen radicals
Renal injury
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Summary:The toxicity of aminoglycosides including gentamicin (GEN), the most widely used drug in this category, is believed to be related to the generation of reactive oxygen species (ROS) in the kidney. Aminoguanidine (AG) is known as an effective antioxidant and its free radical scavenger effects may protect GEN-induced acute renal failure (ARF). Therefore, this study was focused on investigating the possible protective effect of AG against GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue malondialdehyde (MDA) levels; nitric oxide (NO) generation; glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT) activities; glutathione (GSH) content; serum creatinine (Cr) and blood urea nitrogen (BUN) levels. Morphological changes in the kidney were also examined using light microscopy. GEN administration to control group rats increased renal MDA and NO levels but decreased GSH-Px, SOD, CAT activities and GSH content. AG administration with GEN injection resulted in significantly decreased MDA, NO generation and increased GSH-Px, SOD, CAT activities and GSH content when compared with GEN alone. Serum levels of Cr and BUN significantly increased as a result of nephrotoxicity. Also, AG significantly decreased Cr and BUN levels. Morphological changes in the kidney, including tubular necrosis, intracellular edema, glomerular and basement membrane alterations were evaluated qualitatively. Both biochemical findings and histopathological evidence showed that administration of AG reduced the GEN-induced kidney damage. We propose that AG acts in the kidney as a potent scavenger of free radicals to prevent the toxic effects of GEN both at the biochemical and histological level.
ISSN:0065-1281
1618-0372
DOI:10.1016/j.acthis.2006.06.005