L-methionine attenuates gentamicin nephrotoxicity in male Wistar rat: pathological and biochemical findings

Abstract

The clinical uses of gentamicin have so far been restricted due to nephrotoxicity and ototoxicity. The exact mechanism of nephrotoxicity is still unknown; however, it appears that free radicals may be involved. Methionine has previously been shown to alleviate oxidative stress involved in ototoxicity due to its antioxidant properties. Therefore, the effect of methionine supplementation on the gentamicin induced nephrotoxicity was examined in this study. Twenty eight male Wistar rats were randomly divided into 4 equal groups to receive a daily corresponding dose of either gentamicin (80 mg/kg B.W.; i.m.; group GN), Lmethionine (100 mg/kg B.W.; i.p.; MT), combination thereof (MG), and normal saline as control (CT). After slaughtering the animals on day 11, values of blood urea nitrogen (BUN), serum creatinine concentration (SCr), urinary gamma glutamyl transpeptidase (GGT) activity, and renal cortical reduced glutathione (GSH) contents with histopathologic investigations were measured. In group GN, biochemical profiles showed a remarkable increase in BUN, SCr and urinary GGT concentration, and depletion of renal cortical of GSH. In addition, histopathologic studies revealed severe acute tubular necrosis, congestion and hyaline casts, verifying gentamicin-induced nephrotoxicity. In group MG, only mild epithelial changes and renal congestion were prominent findings. Moreover, these changes in rats given the combined therapy (MG) were significantly less than those of group GN, thereby suggesting that supplemented L-methionine ameliorate gentamicin nephrotoxicity in rat. In group MT, only medullary congestion was seen without change in the biochemical factors as was in the CT group with normal kidney structure. Generally, results of this study showed that methionine may significantly prevent gentamicin nephrotoxicity, removing the oxidative stress.