Comparative ototoxicity of gentamicin in the guinea pig and two strains of rats.

Gentamicin ototoxicity and nephrotoxicity were compared in two strains of rats, Sprague-Dawley and Fisher-344, and in the Hartley albino guinea pig. Treatment groups consisting of 8 male rats of each strain and four male guinea pigs were dosed subcutaneously for 14 days with either 80 or 100 mg/kg of gentamicin sulfate in saline. Brainstem auditory evoked response (BAER) thresholds were recorded from each animal in each group on day 11 post-administration. Blood urea-nitrogen and serum creatinine were measured in blood obtained on day 11 post-administration as measures of nephrotoxicity. Kidney weight/body weight ratios were also determined. Loss of sensory hair cells was observed in the basal region of the organ of Corti from all animals treated with 100 mg/kg of gentamicin. The hair cell loss and BAER threshold elevations were greatest in the guinea pigs. Fisher-344 rats showed more extensive hair loss and greater BAER threshold elevations than Sprague-Dawley rats. The Fisher-344 rats exhibited increased blood urea-nitrogen and kidney weight/body weight ratios. Sprague-Dawleys did not suffer any nephrotoxic effects. These data indicate that the Fisher-344 rat is useful animal in which to study aminoglycoside ototoxicity as it exhibits both functional and morphological changes after gentamicin administration.