IRON CHELATORS PROTECT FROM AMINOGLYCOSIDE-INDUCED COCHLEO-TOXICITY AND VESTIBULO-TOXICITY

The attenuation of gentamicin-induced hearing loss by iron chelators a nd radical scavengers has recently been demonstrated in guinea pig in vivo. The present study investigated whether this protective treatment is effective against hearing loss and vestibular damage caused by oth er aminoglycosides. In a direct comparison, dihydroxybenzoate was chos en over deferoxamine because of its more effective action against gent amicin-induced hearing loss. Guinea pigs received daily injections of kanamycin (250 mg/kg/d) or streptomycin (300 mg/kg/d) for 23 d to indu ce severe cochlear or vestibular toxicity, respectively. Kanamycin inj ections resulted in a progressive threshold shift of 60 to 80 dB at 18 kHz, while streptomycin injections induced only a small threshold shi ft. In contrast, streptomycin abolished almost all vestibular response s. Coinjection of aminoglycosides with a mixture of dihydroxybenzoate (100 mg/kg/d) and mannitol (30 mg/kg/d) significantly attenuated kanam ycin-induced hearing loss and protected against streptomycin-induced v estibulotoxicity. DHB/mannitol did not affect serum levels or the anti bacterial efficacy of either aminoglycoside. This study supports the i dea that iron and free radicals play a critical role in the toxic side effects of aminoglycoside antibiotics. Furthermore, the previously pr oposed therapeutic protection is not limited to gentamicin but applica ble to other aminoglycosides as well. (C) 1998 Elsevier Science Inc.