Effect of sex hormones on gentamicin-induced nephrotoxicity in rats

1. There is clinical and experimental evidence that females are more susceptible to gentamicin-induced nephrotoxicity. To assess the role of sex as a risk factor in aminoglycoside-related acute renal failure 16 groups of five 120 +/- 15-day old (young adult) Wistar rats of both sexes, castrated and non-castrated, were treated with gentamicin. These rats were medicated with 40 mg kg-1 24 h-1 gentamicin alone for 10 days. Some animals received gentamicin after 5 days of treatment with depot testosterone or estrogens. 2. Blood urea and creatinine levels before and after gentamicin administration were measured to evaluate renal function. Histological lesions were studied by light microscopy by two pathologists who were unaware of the group. Rats with normal or elevated levels of estrogens showed functional impairment after gentamicin. A poor correlation was detected between levels of urea/creatinine and histopathological findings. 3. Lesions were considerably more severe in females. Testosterone administration to intact animals offered partial protection against the renal effects of gentamicin in both sexes. In contrast, estradiol administered to intact animals was regularly associated with significantly more severe lesions in both males and females. Castration by itself attenuated the gentamicin-induced renal alterations in males, but not in females. These data provide support for an unfavorable effect of estrogens rather than a favorable effect of testosterone. The demonstration of more severe lesions in female castrated rats when compared with male castrated rats indicates the participation of other factors, possibly of a genetic nature, in the pathogenesis of gentamicin-induced renal lesions.