Protection against aminoglycoside otic drop-induced ototoxicity by a spin trap: I. Acute effects

Topical administration of aminoglycoside antibiotic drops containing neomyc in and polymyxin B disrupts cochlear structure and function in rodents, pos sibly as a result of reactive oxygen species generation. This study investi gated the ability of a spin trap, alpha-phenyl-tert-butyl-nitrone (PBN), to prevent acute aminoglycoside antibiotic drop-induced cochlear dysfunction. Guinea pigs were monitored for compound action potential thresholds and 1. 0 mu V root-mean-square cochlear microphonic isopotential curve values, the n injected intraperitoneally with PEN (60 mg/kg) or saline solution. After 10 minutes, 50 mu l of PEN (100 mmol/L) or artificial perilymph was applied to the round window membrane, followed after 10 minutes with artificial pe rilymph or aminoglycoside antibiotic drops (50 mu l). From 10 to 60 minutes after exposure, mean compound action potential thresholds progressively in creased in the artificial perilymph-aminoglycoside antibiotic drop group, b eginning with high frequencies and later including ever-lower frequencies. These threshold shifts in compound action potentials were significantly gre ater (p < 0.05) than those seen in the artificial perilymph-artificial peri lymph or PBN-aminoglycoside antibiotic drop groups. This finding indicates that PEN provided protection against acute aminoglycoside antibiotic drop-i nduced compound action potential threshold sensitivity loss. Mean cochlear microphonic shift values at 60 minutes in the artificial perilymph-aminogly coside antibiotic drop group significantly exceeded those of the other grou ps only at the highest frequencies. These data suggest that acute aminoglyc oside antibiotic drop-induced cochlear disruption primarily affects high fr equency compound action potential function and may be partially reactive ox ygen species-mediated and preventable.