Aminoglycoside ototoxicity in adult CBA, C57BL and BALB mice and the Sprague-Dawley rat

The availability of genetic information, transgenic and knock-out animals m ake the mouse a primary model in biomedical research. Aminoglycoside ototox icity, however, has rarely been studied in mature mice because they are con sidered highly resistant to the drugs. This study presents models for kanam ycin ototoxicity in adult CBA/J, C57BL/6 and BALB/c mouse strains and a com parison to Sprague-Dawley rats. Five-week-old mice were injected subcutaneo usly twice daily with 400-900 mg kanamycin base/ kg body weight for 15 days . Kanamycin induced dose-dependent auditory threshold shifts of up to 70 dB at 24 kHz as measured by auditory brain stem-evoked responses. Vestibular function was also affected in all strains. The functional deficits were acc ompanied by hair cell loss in both cochlear and vestibular neurosensory epi thelia. Concomitant administration of the antioxidant 2,3-dihydroxybenzoate significantly attenuated the kanamycin-induced threshold shifts. In adult male Sprague-Dawley rats, doses of 1 X 500 mg or 2 X 300 mg kanamycin base/ kg body weight/day X 14 days induced threshold shifts of approximately 50 d B at 20 kHz. These were accompanied by loss of outer hair cells. The order of susceptibility, BALB > CBA > C57, was not due to differences in the phar macokinetics of kanamycin. It also did not correlate with the presence of A hllAhl2 genes which predispose C57 and BALB strains, respectively, to accel erated age-related hearing loss. Pigmentation, however, paralleled this ran k order suggesting an influence of melanin on cochlear antioxidant status. (C) 2001 Published by Elsevier Science B.V.