Protective role of aminoguanidine on gentamicin-induced acute renal

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 GEN-induced nephrotoxicity in an in vivo rat model. We investigated the effects of AG on GEN-induced changes in renal tissue matondialdehyde (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 atone. 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. (c) 2006 Elsevier GmbH. All, rights reserved.

C1 Inonu Univ, Fac Med, Dept Pharmacol, TR-44280 Malatya, Turkey.

Inonu Univ, Fac Med, Dept Physiol, TR-44280 Malatya, Turkey.

Under Secretariat Customs Directorate Gen Customs, Republ Turkey Prime Minist, Ankara, Turkey.

Inonu Univ, Fac Med, Dept Histol, TR-44280 Malatya, Turkey.