Protection against Aminoglycoside Otic Drop-Induced Ototoxicity by a Spin Trap: I. Acute Effects

Abstract

Topical administration of aminoglycoside antibiotic drops containing neomycin and polymyxin B disrupts cochlear structure and function in rodents, possibly as a result of reactive oxygen species generation. This study investigated the ability of a spin trap, α-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 μV root-mean-square cochlear microphonic isopotential curve values, then injected intraperitoneally with PBN (60 mg/kg) or saline solution. After 10 minutes, 50 μl of PBN (100 mmol/L) or artificial perilymph was applied to the round window membrane, followed after 10 minutes with artificial perilymph or aminoglycoside antibiotic drops (50 μl). From 10 to 60 minutes after exposure, mean compound action potential thresholds progressively increased in the artificial perilymph-aminoglycoside antibiotic drop group, beginning with high frequencies and later including ever-lower frequencies. These threshold shifts in compound action potentials were significantly greater (p < 0.05) than those seen in the artificial perilymph-artificial perilymph or PBN-aminoglycoside antibiotic drop groups. This finding indicates that PBN provided protection against acute aminoglycoside antibiotic drop-induced compound action potential threshold sensitivity loss. Mean cochlear microphonic shift values at 60 minutes in the artificial perilymph-aminoglycoside antibiotic drop group significantly exceeded those of the other groups only at the highest frequencies. These data suggest that acute aminoglycoside antibiotic drop-induced cochlear disruption primarily affects high frequency compound action potential function and may be partially reactive oxygen species-mediated and preventable