EFFECT OF SEX-HORMONES ON GENTAMICIN-INDUCED NEPHROTOXICITY IN RATS

1. There is clinical and experimental evidence that females arc more s usceptible 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 s exes, castrated and non-castrated, were treated with gentamicin. These rats were medicated with 40 mg kg-1 24 h-1 gentamicin alone for 10 da ys. Some animals received gentamicin after 5 days of treatment with de pot testosterone or estrogens. 2. Blood urea and creatinine levels bef ore and after gentamicin administration were measured to evaluate rena l function. Histological lesions were studied by light microscopy by t wo pathologists who were unaware of the group. Rats with normal or ele vated levels of estrogens showed functional impairment after gentamici n. A poor correlation was detected between levels of urea/creatinine a nd histopathological findings. 3. Lesions were considerably more sever e in females. Testosterone administration to intact animals offered pa rtial 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 fe males. Castration by itself attenuated the gentamicin-induced renal al terations 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 castr ated rats when compared with male castrated rats indicates the partici pation of other factors, possibly of a genetic nature, in the pathogen esis of gentamicin-induced renal lesions.