Protective effect of metformin against gentamicin induced nephrotoxicity in rabbits

Gentamicin is used against gram negative infections, but major problem encountered is nephrotoxicity that occurs in 10-20% of therapeutic regimes. Gentamicin induced oxidative stress plays an important role in this nephrotoxicity. Recent data has shown metformin to possess antioxidant activity. Purpose of study was to evaluate potential role of metformin in protecting kidney from nephrotoxicant insult. Thirty-six rabbits were randomly divided into six groups (n=6). G-1 received 1 ml isotonic saline intraperitoneally (IP) daily for 13 days. G-2 received gentamicin (150 mg/kg/day) IP for last 6 days of 13 days. G-3 received gentamicin (40 mg/kg/day) IP for 13 days. G-4 received metformin salt (100 mg/kg/day) dissolved in drinking water via feeding tube for 13 days. G-5 received metformin salt (100 mg/kg/day) via feeding tube for 13 days plus gentamicin (150mg/kg/day) IP for last 6 days of 13 days. G-6 received gentamicin (40mg/kg/day) IP plus metformin salt (100mg/kg/day) via feeding tube for 13 days. Blood was collected on days 0 and 14 for serum urea & creatinine estimation. All animals were sacrificed and kidneys were removed for renal histological examination. Metformin showed nephroprotective effect. It blunted nephrotoxic insult at 150mg/kg/day of gentamicin, whereas showed complete nephroprotection at 40mg/kg/day of gentamicin. Metformin offers complete nephroprotection at low toxic dose ranges of gentamicin. This could offer an efficacious and cheaper treatment alternative in those diabetics who also suffer from gram-negative infections.