Carnosine protects against gentamicin-induced nephrotoxicity in rats

ABSTRACT

Acute renal failure is a major complication of gentamicin, limiting use of this antibiotic in treatment of gram negative infections. Reactive oxygen species are hypothesized to be a major factor in the nephrotoxicity of gentamicin and measures controlling this oxidative damage are widely appreciated. This work was conducted to test the hypothesis that treatment with carnosine, a biological antioxidant, may prevent or ameliorate acute renal injury, using a rat model of gentamicin-induced nephrotoxicity. Male wistar albino rats were assigned to one of six treatment groups; group I [control] rats were given normal saline injections daily for 10 days; group II rats were given IM gentamicin injections, 100 mg/kg/day, for 6 days group III, IV and V rats were given gentamicin, together with IP carnosine injections 50, 100 and 200 mg/kg/day, respectively, for 10 days starting 4 days before gentamicin injections; and group VI rats were given only carnosine 200 mg/kg/day, for 10 days. All rats were weighed before and after experimentation, and 24 hour urine volume were collected in metabolic cages. At end of study, blood samples were collected for measurement of BUN, creatinine level and creatinine clearance. Rats were then sacrificed and the kidneys were excised. The left kidneys were homogenized and used for biochemical determination of MDA, GPX and SOD, while the right kidneys were processed for histological examination and scoring of renal cortical pathology. Results showed that gentamicin produced evident nephrotoxic effects revealed by; increased kidney weight, increased urine volume, elevations of serum levels of BUN and creatinine and decreased creatinine clearance; together with increased MDA, reduced GPX and SOD in kidney tissues. Marked histological alterations were also evident in the renal cortex [acute tubular necrosis of grade 2-3]. Carnosine treatment leads to significant dose-related attenuation of nephrotoxic effects of gentamicin revealed by reduction of the elevated biochemical parameters, improved oxidative status in the kidney, and amelioration of the histological changes. It is concluded that carnosine treatment could ameliorate the severity of renal cortical necrosis induced by gentamicin and maintain a better renal function. Thus, carnosine may be a useful candidate in the combination therapy with gentamicin to limit free radical-mediated renal injury