Tehran University Medical Journal

Background: In recent publications, several mechanisms have been implicated in gentamicin (GM) nephrotoxicity. Reactive oxygen species have been proposed as one of the causative factors of the drug renal side effects. This study was designed to evaluate the protective effects of the antioxidant vitamins against GM-mediated nephropathy in insitu isolated rat kidneys.

Methods: Male Sprague-Dawley rats were randomly assigned to one of the following groups of seven rats: Group 1 (control) was tyrode perfused kidneys. Group 2 (GM), 200µg/ml gentamicin was added to the perfusate. Group 3 (GM + Vit C), the same as group 2 but vitamin C (200 mg/L) was added to the drinking water for 3 days and 100 mg/L to the perfusate. Group 4 (GM + Vit E), the same as group 2 but vitamin E (100 mg/100 g BW, ip) was injected 12 h before experiments. Group 5 (GM + Vit C + Vit E) the same as group 2 but Vit E and C were co-administered (same as Group 3 & 4). Urinary N-acetyle-B-D-glucosaminidas (NAG) and renal cortex superoxide dismutase (SOD) levels were measured and tissue histological evaluations were performed.

Results: Gentamicin caused a significant nephrotoxicity demonstrated by increase in urinary NAG. Decline in SOD contents were observed comparing to controls. Vit C or Vit E inhibited the gentamicin-induced increased releases of NAG into urine but did not show a significant effect on the SOD levels.  

Conclusion: Co-administration of VitC&E significantly prevented the GM nephrotoxicity demonstrating by preservation of SOD levels and prevention of increase in urinary enzyme activities. Histological studies of renal tissues provided additional evidences for protective effects of antioxidant vitamins. We concluded that moderate doses of Vit C & E have protective effects in gentamicin nephrotoxicity and co-administration of these vitamins have additional beneficial effects.