Carnosine Protects Against Gentamicin-induced Nephrotoxicity in Rats

Background: Acute renal failure is a major complicationof gentamicin, limiting use of this antibiotic in treatment ofgram negative infections. Reactive oxygen species are hypothesizedto be a major factor in the nephrotoxicity of gentamicinand measures controlling this oxidative damage are widelyappreciated.Objective: This work was conducted to test the hypothesisthat treatment with carnosine, a biological antioxidant, mayprevent or ameliorate acute renal injury, using a rat model ofgentamicin-induced nephrotoxicity.six treatment groups; group I (control) rats were givennormal saline injections daily for 10 days; group II rats weregiven IM gentamicin injections, 100 mg/kg/day, for 6 days;group III, IV and V rats were given gentamicin, together withIP carnosine injections 50,100 and 200 mg/kg/day, respectively,for 10 days starting 4 days before gentamicin injections; andgroup VI rats were given only carnosine 200 mg/kg/day, for10 days. All rats were weighed before and after experimentation,and 24 hour urine volume were collected in metaboliccages. At end of study, blood samples were collected formeasurement of BUN, creatinine level and creatinine clearance.Rats were then sacrificed and the kidneys were excised. The left kidneys were homogenized and used for biochemicaldetermination of MDA, GPX and SOD, while the right kidneyswere processed for histological examination and scoring ofrenal cortical pathology.Results: Results showed that gentamicin produced evidentnephrotoxic effects revealed by; increased kidney weight,increased urine volume, elevations of serum levels of BUNand creatinine and decreased creatinine clearance; togetherwith increased MDA, reduced GPX and SOD in kidney tissues.Marked histological alterations were also evident in the renalcortex (acute tubular necrosis of grade 2-3). Carnosine treatmentleads to significant dose-related attenuation ofnephrotoxic effects of gentamicin revealed by reduction ofthe elevated biochemical parameters, improved oxidative status in the kidney, and amelioration of the histologicalchanges.Conclusion: It is concluded that carnosine treatment couldameliorate the severity of renal cortical necrosis induced bygentamicin and maintain a better renal function. Thus, carnosinemay be a useful candidate in the combination therapy withgentamicin to limit free radical-mediated renal injury.