title: Topical aminoglycoside ototoxicity: attempting to protect the cochlea.
abstract: Cochlear damage following topical application of aminoglycoside antibiotics to the round window membrane is a recognized phenomenon in both animal experiments and clinical reports. The authors have recently reported the ability of the free radical scavenging agent, alpha lipoic acid, to protect against the cochleo-toxic side effects of systemically administered aminoglycoside antibiotics. This study attempts to determine if the protective effect of this free radical scavenging agent is also seen following topical aminoglycoside application. Animals were implanted with osmotic pumps which delivered 2.5 microl/h solution of either neomycin 5% or neomycin plus alpha lipoic acid (50 mg/ml). Control animals received normal saline solution. Drug solutions were presented directly to the round window membrane over a 7-day period. Auditory sensitivity was monitored using compound action potentials (CAPs) of the auditory nerve recorded through an implanted chronic electrode terminating at the round window. Sixteen animals were entered into the study and randomized to one of the above groups. All animals receiving neomycin solution, with or without alpha lipoic acid, maintained normal thresholds for the first 3 days of the treatment period. Animals receiving neomycin solution alone experienced profound and rapid deterioration in auditory sensitivity, which was maximal by day 6. Animals receiving neomycin plus alpha lipoic acid also experienced significant cochlear damage; however, the rate of deterioration was slower than that seen in the group receiving neomycin alone. All control animals receiving saline maintained good hearing thresholds throughout the treatment period.
authors.affiliation: Hearing Research Laboratories, Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, North Carolina, USA. bconlon@iol.ie
authors.forename: B J
authors.initials: BJ
authors.lastname: Conlon
authors.forename: D W
authors.initials: DW
authors.lastname: Smith
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000378:metabolism*; D001307:Auditory Perception / Q000187:drug effects; D015834:Cochlear Diseases / Q000139:chemically induced* / Q000517:prevention & control*; D004334:Drug Administration Schedule; D005071:Evoked Potentials / Q000502:physiology; D016166:Free Radical Scavengers / Q000494:pharmacology*; D006168:Guinea Pigs; D009355:Neomycin / Q000009:adverse effects* / Q000378:metabolism*; D012405:Round Window, Ear / Q000187:drug effects; D012680:Sensitivity and Specificity; D008063:Thioctic Acid / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D016166:Free Radical Scavengers; D008063:Thioctic Acid; D009355:Neomycin