doi: 10.1111/j.1472-8206.2010.00900.x ORIGINAL ARTICLE The protective effect of eugenol against gentamicin-induced nephrotoxicity and oxidative damage in rat kidney Mahmoud Mohamed Said* Department of Biochemistry, Faculty of Science, Ain Shams University, Cairo, 11566, Egypt INTRODUCTION Gentamicin (GM) is an aminoglycoside antibiotic which is commonly used for the treatment of infections caused by Gram-negative bacteria [1]. The bactericidal activity of GM is derived from its ability to bind prokaryotic ribosomes. This action blocks the ribosomal initiation complex and/or causes mistranslation. As a result, protein synthesis is inhibited or deranged, causing bacterial death [2]. However, complications attributable to aminoglycoside toxicity rank as one of the most common reasons for prolonging hospital stays in the developed world [3], as it has been estimated that up to 30% of patients treated with GM for more than 7 days show some signs of nephrotoxicity [4]. Gentamicin is not metabolized in the body but is essentially eliminated by glomerular filtration and par- tially reabsorbed by proximal tubular cells [5]. No conclusive evidence exists of tubular secretion of GM, and consequently most aminoglycosides excreted in the urine correspond to filtrates [6]. Genatamicin-induced nephrotoxicity is characterized by direct proximal tubular necrosis [5]. The specificity of GM for renal toxicity is apparently related to its Keywords eugenol, gentamicin, nephrotoxicity, oxidative stress Received 23 May 2010; revised 13 September 2010; accepted 11 October 2010 *Correspondence and reprints: mahsaid74@hotmail.com ABSTRACT Gentamicin (GM) is an effective aminoglycoside antibiotic against life-threatening Gram-negative bacteria. However, a major complication of therapeutic doses of GM is nephrotoxicity, which is believed to be related to the generation of reactive oxygen species. The present study was therefore aimed to investigate the protective effect of eugenol, a phenolic antioxidant, on GM-induced nephrotoxicity in Sprague–Dawley rats. Intramuscular injection of rats with GM (80 mg/kg body weight/day) for six consecutive days induced marked acute renal failure, manifested by a sharp significant increase in serum urea and creatinine levels, along with a significant depletion of serum potassium level, compared to normal controls. GM-induced renal dysfunction was attributable to enhanced oxidative stress, as revealed by decreased superoxide dismutase and catalase activities, glutathione depletion and increased lipid peroxidation. Furthermore, kidney lactate dehydrogenase activity, as an indicator of hypoxia, was significantly increased by GM administration. Eugenol (100 mg/kg body weight, per os) administered four days before and six days concurrently with GM (80 mg/kg body weight, i.m.) restored normal renal functions and suppressed GM-induced oxidative stress and hypoxia. Light microscopical examination of the renal tissues of GM-treated animals demonstrated severe tubular necrosis at the cortex and increased cellular inflammatory processes. However, these alterations were considerably reduced with eugenol coadministration. In conclusion, eugenol ameliorates GM-induced nephrotoxicity and oxidative damage by scaveng- ing oxygen free radicals, decreasing lipid peroxidation and improving intracellular antioxidant defense. ª 2010 The Author Fundamental and Clinical Pharmacology ª 2010 Socie ´ te ´ Franc ¸aise de Pharmacologie et de The ´ rapeutique 708 Fundamental & Clinical Pharmacology 25 (2011) 708–716 Fundamental & Clinical Pharmacology