The protective effect of taurine against gentamicin-induced acute tubular necrosis in rats.

摘要

BACKGROUND: Taurine, which is the major intracellular free beta-amino acid, is known to be an endogenous antioxidant and a membrane-stabilizing agent. In this study, we wished to know whether taurine altered the concentration of gentamicin in kidney tissue and could protect against gentamicin-induced acute proximal tubular injury. METHODS: Wistar albino rats of both sexes were assigned to three groups, which all received one of the following daily intraperitoneal injections for 8 days: (i) 0.9% sodium chloride (NaCl) alone at the same volume as gentamicin treated rats (group C; n=8); (ii) 100 mg/kg/day gentamicin alone (group G; n=8, four male, four female); or (iii) 100 mg/kg/day gentamicin plus 7.5 ml/kg/day taurine (group G+T; n=9, five male, four female). Urine was collected for 24 h for the determination of urine volume and creatinine. Intracardiac blood was collected for blood urea nitrogen (BUN) and serum creatinine determination. The kidneys were removed, weighed, and the left kidneys were subjected to biochemical analysis for the determination of thiobarbituric acid-reactive substance (TBARS) and lactate levels, and glutathione peroxidase (Gpx) and superoxide dismutase (SOD) activities. The right kidneys were divided vertically in half. The upper halves were used for histopathological examination, by light and electron microscopy. The lower halves were used to detect the gentamicin concentration within the kidney tissue, by high-performance liquid chromatography (HPLC). Changes in body weight and normalized kidney weight were recorded. RESULTS: Taurine treatment reduced gentamicin-induced increases in serum creatinine, 24 h urine volume, BUN and tissue lactate and TBARS levels (0.57+/-0.02 vs 1.06+/-0.08 mg/dl, P<0.001; 9.00+/-1.46 vs 20.9+/-2.73 ml, P<0.001; 25.3+/-1.87 vs 54.1+/-6.99 mg/dl, P<0. 001; 2.56+/-0.10 vs 3.44+/-0.08 micromol/g wet tissue, P<0.001; and 66.4+/-3.41 vs 79.5+/-5.07 nmol/g wet tissue, P>0.05, respectively). Taurine reduced the accumulation of gentamicin within the kidney tissue (233+/-29 vs 494+/-93 microg/g wet tissue, P<0.05). Taurine treatment also prevented body weight loss due to gentamicin administration (17.8+/-1.64 vs -10.0+/-7.08 g, P<0.01) and normalized reduced Gpx and SOD activities (3.46+/-0.16 vs 2.37+/-0. 15 U/g wet tissue, P<0.01; and 15577+/-377 vs 12662+/-577 U/g wet tissue, P<0.01, respectively). Light microscopic examination of the renal tissues from gentamicin-treated rats revealed severe histopathological changes, whereas specimens obtained from taurine-treated rats revealed only mild changes. This finding was supported by electron microscopic examination. CONCLUSIONS: Our observations suggest that taurine treatment attenuates the accumulation of gentamicin within kidney tissue and counteracts the deleterious effect of gentamicin on renal tubular function. They may have potentially important clinical implications.