Abstract:
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 GENinduced
nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GENinduced
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.
