Salicylate attenuates gentamicin-induced ototoxicity

Aminoglycosides, primarily gentamicin, are the most commonly used antibioti cs worldwide despite their toxicity to the kidney and the inner ear. A prev entive therapy against these side effects should combine safety and efficac y with low cost because aminoglycoside-induced deafness is most prevalent i n developing countries. We have previously shown that aminoglycosides catal yze the formation of free radicals in an iron-dependent reaction and have d elineated the structure of an iron-gentamicin complex. Here we demonstrate that 2-hydroxybenzoate (salicylate), which can act as an iron chelator and antioxidant, effectively protects against gentamicin-induced hearing toss i n guinea pigs. Co-therapy with salicylate reduced a profound gentamicin-ind uced auditory threshold shift of more than 60 dB to less than 20 dB. Morpho logical assessment of the inner ear confirmed protection of auditory sensor y cells. Salicylate altered neither serum levels of gentamicin nor its anti bacterial efficacy. Because the required salicylate levels correspond to an ti-inflammatory revels in humans, this treatment holds promise for clinical application.