Sex-related differences in the susceptibility of rats to gentamicin nephrotoxicity

Age-matched male and female Fischer 344 rats were treated with gentamicin, 40 mg/kg of animal body weight per day, for three to 21 days. Renal dysfunction was less severe in females as measured by concentrations of blood urea nitrogen and creatinine and by cortical slice uptake of p-aminohippuric acid and N1-methylnicotinamide chloride. Also, cortical concentrations of gentamicin in females were lower than in males. Neither exogenous testosterone administered to adult females nor castration of prepubertal males changed the pattern of dysfunction. These results show that sex affects susceptibility to aminoglycoside nephrotoxicity by mechanisms that are undefined but that are apparently unrelated to testosterone. The variable of sex needs to be considered in interpreting the results of studies of experimental aminoglycoside nephrotoxicity.