Gentamicin (GM) is an antibiotic widely used in treating severe gram-negative infections. However, its clinical use is limited by its nephrotoxicity. Several lines of evidence indicate that free radicals are important mediators of gentamicin nephrotoxicity. Therefore, the aim of this work was to investigate the possible protective effect of the flavonoid quercetin, an antioxidant, on gentamicin-induced nephrotoxicity. For this purpose, rats were divided into four groups. First group served as a control and injected with the normal saline, second group was injected with quercetin (50 mg/kg/d, per os) for 7 d, third group was injected with gentamicin (80 mg/kg/d, intraperitoneally) for 7 d and the fourth group of animals was injected with quercetin plus gentamicin simultaneously for 7 d. Total protein levels were estimated in 24-h urine samples to assess kidney dysfunction. The rats were sacrificed on the seventh day and kidneys were collected for histopathological studies. Blood urea nitrogen (BUN) and creatinine levels were measured in the blood. Moreover, glutathione (GSH), lipid peroxide (TBARS) levels, superoxide dismutase (SOD) and catalase (CAT) activities were determined in renal tissues. GM-treated rats showed early kidney dysfunction as urinary total protein, BUN and serum creatinine levels were significantly increased. The significant decrease in GSH levels, SOD, CAT activities and increase in TBARS levels, indicated that GM-induced nephrotoxicity was mediated through oxidative stress reactions. Histopathological examination of GM-treated rats revealed degenerative changes in glomeruli and tubules. On the other hand, simultaneous administration of quercetin plus gentamicin protected kidney tissues against nephrotoxic effects of gentamicin as evidenced from amelioration of histopathological changes and normalization of kidney biochemical parameters.
2009 The Pharmaceutical Society of Japan