Salicylate attenuates gentamicin-induced ototoxicity.
Aminoglycosides, primarily gentamicin, are the most commonly used antibiotics worldwide despite their toxicity to the kidney and the inner ear. A preventive therapy against these side effects should combine safety and efficacy with low cost because aminoglycoside-induced deafness is most prevalent in developing countries. We have previously shown that aminoglycosides catalyze the formation of free radicals in an iron-dependent reaction and have delineated 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 loss in guinea pigs. Co-therapy with salicylate reduced a profound gentamicin-induced auditory threshold shift of more than 60 dB to less than 20 dB. Morphological assessment of the inner ear confirmed protection of auditory sensory cells. Salicylate altered neither serum levels of gentamicin nor its antibacterial efficacy. Because the required salicylate levels correspond to anti-inflammatory levels in humans, this treatment holds promise for clinical application.
Kresge Hearing Research Institute, Department of Otolaryngology, University of Michigan, Ann Arbor 48109-0506, USA.
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D000284:Administration, Oral; D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use*; D001309:Auditory Threshold / Q000187:drug effects*; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005839:Gentamicins / Q000037:antagonists & inhibitors* / Q000633:toxicity; D006168:Guinea Pigs; D007502:Iron Chelating Agents / Q000627:therapeutic use*; D008297:Male; D008826:Microbial Sensitivity Tests; D020156:Salicylic Acid / Q000627:therapeutic use*
D000975:Antioxidants; D005839:Gentamicins; D007502:Iron Chelating Agents; D020156:Salicylic Acid