Sex difference in the susceptibility of rats to gentamicin nephrotoxicity: Influence of gonadectomy and hormonal replacement therapy

Objective: The aims were to find out the influence of sex on the renal toxicity of gentamicin (G) in Sprague-Dawley rats and whether castration or ovariectomy (with or without hormonal replacement therapy) would affect the nephrotoxicity. Methods: G was given intramuscularly (80 mg/kg/day for 6 days) to intact and gonadectomized male and female rats, with or without testosterone (2 mg/kg/day for 15 days) in males, or estradiol (80 μg/kg/day for 15 days) in females. Nephrotoxicity was assessed by histopathology of the renal cortex and by measuring urea and creatinine concentrations in plasma. Results: G induced significant increase in the concentration of creatinine and urea in plasma. This effect was more marked in males than in females. Histologically, however, the degree of renal proximal renal necrosis in both sexes was similar. Castrated rats treated with G had signicantly lower concentrations of creatinine and urea than their sham-operated counterparts. The renal histology and creatinine and urea values obtained from castrated rats treated with testosterone and G were not significantly different from that in castrated rats treated with G alone. Estradiol administration in ovarectomized rats treated with G caused significantly lower plasma concentrations of creatinine and urea. Testosterone or estradiol, given alone at the above doses, did not significantly affect the renal histology or plasma creatinine and urea levels. Conclusions: The above results suggest the presence of a small sex-related difference in the susceptibility of Sprague-Dawley rats to G nephrotoxicity. Treatment with testosterone in castrated rats and estradiol in ovarectomized animals did not significantly alter the toxicity.