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

Abstract

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.

Round window gentamicin application: an inner ear hair cell damage protocol for the mouse

“…This is particularly true when very early events following hair cell damage are of interest. Because systemic aminoglycoside injections in mammals are limited by toxicity, lower doses given over an extended period of time are often necessary before hair cell damage is obtained (Wu et al, 2001;Forge and Shacht, 2000;Sullivan et al, 1987). This results in gradual injury to the sensory epithelium and interferes with attempts to pinpoint the stages of cellular change in time and to study the earliest events following damage.…”

“…Application methods used to date have included systemic injection and local application via trans-tympanic injection, endolymphatic sac injection, and intracochlear perfusion (Sullivan et al, 1987;Kimura et al, 1988;Lee and Kimura, 1991;Wanamaker et al, 1998;Dodson, 1997). Although systemic injection has been a particularly useful application method in some species, it has limitations in the mouse.…”

Mitochondria-Targeted Antioxidant MitoQ Reduces Gentamicin-Induced Ototoxicity

“…Here, we evaluated the use of MitoQ, a mitochondriatargeted derivative of the antioxidant CoQ 10 , as a potent and novel therapeutic agent for the prevention of cochlear cell damage and hearing loss induced by the AG gentamicin, which is cochleotoxic in guinea pigs (28).…”

Editorial

“…Similarly, a dose of 40 mg/kg gentamicin produced nephrotoxicity in F344 rats while a dose of 70-100 mg/kg was required to induce an equivalent adverse effect in Sprague-Dawley animals, and male F344 rats were more susceptible than females to gentamicin-induced renal damage (Goodrich & Hottendorf, 1995;Sugarman et al, 1983;Kacew, 1989;Kacew & Bergeron , 1990). Sullivan et al (1987) reported that Sprague-Dawley rats were more resistant to the nephrotoxic and ototoxic effect of gentamicin than F344 animals. A decreased susceptibility to the nephrotoxic action of gentamicin in Sprague-D aw ley rats w as supported by the observation that proteinuria occurre d after 4 d in Wistar rats, whereas in Sprague-D awley animals 9-10 d was needed to produce this adverse effect (Smetana et al, 1988(Smetana et al, , 1992.…”