Role of antidiabetic agents in protecting the kidneys from oxidant insult in rabbits

Objective: To compare the antioxidant potential of insulin sensitizers in protecting kidneys from gentamicin induced oxidant insult. Methodology: The work was done at department of Pharmacology & Therapeutics, Army Medical College, Rawalpindi. Thirty six rabbits were taken and randomly divided into six groups. G-1 (control group) was administered intraperitoneally (IP) 1 ml of isotonic saline daily for 13 days. G-2 was given gentamicin (40 mg/kg) IP daily for 13 days. G-3 was given metformin salt (100 mg/kg) dissolved in drinking water through feeding tube for 13 days. G-4 was administered pioglitazone salt (10 mg/kg) dissolved in drinking water through feeding tube for 13 days. G-5 received metformin salt (100 mg/kg/day) through feeding tube plus gentamicin (40 mg/kg) IP for 13 days. G-6 received pioglitazone salt (10 mg/kg/day) through feeding tube plus gentamicin (40 mg/kg/day) IP for 13 days. Blood samples were taken on days 0 and 14 for BUN & creatinine estimation. All rabbits were sacrificed on day 14 and their kidneys were taken out for renal histological examination. Results: Among the two drugs, only Metformin showed nephroprotective effect. The biochemical markers; BUN and serum creatinine remained within normal range i.e. 6.96+0.24 mmol/l & 102.16±11.05 µmol/l, respectively in group 5 which received metformin along with gentamicin. Likewise their renal histology was also normal without any signs of necrosis. On the other hand Pioglitazone failed to exhibit any nephroprotection as evident by the highly deranged BUN (12.81+0.64 mmol/l) and serum creatinine (141.33±4.56 µmol/l) levels of the rabbits of group 6 which received pioglitazone and gentamicin. Their renal histological exam also showed necrosis. Conclusion: Metformin protects kidneys against gentamicin induced renal oxidant toxicity.