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 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.
Polat
Alaadin
A
Department of Physiology, Faculty of Medicine, Inonu University, Malatya, Turkey.
Parlakpinar
Hakan
H
Tasdemir
Seda
S
Colak
Cemil
C
Vardi
Nigar
N
Ucar
Muharrem
M
Emre
Memet Hanifi
MH
Acet
Ahmet
A
D058186:Acute Kidney Injury / Q000139:chemically induced* / Q000473:pathology*; D000818:Animals; D005260:Female; D005839:Gentamicins / Q000494:pharmacology*; D006146:Guanidines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D005839:Gentamicins; D006146:Guanidines; C004479:pimagedine