The effects of sound conditioning on gentamicin-induced vestibulocochlear toxicity in gerbils.

OBJECTIVES/HYPOTHESIS: Recent studies in animal models have shown via physiologic and histologic measures that the administration of exogenous antioxidants is protective against gentamicin-induced oto-vestibulo toxicity. In addition, studies have also shown that sound conditioning increases cochlear antioxidants. The objective of this study is to determine whether sound conditioning provides protection against gentamicin in the cochlear and/or vestibular system. STUDY DESIGN: : Prospective animal study. METHODS: Three-month-old gerbils were divided into three groups (A, B, and C). The gerbils in group A were sound conditioned only (n = 2). In group B, the animals received gentamicin on the round window (n = 2). The gerbils in group C were sound conditioned first and later received gentamicin to the round window (n = 2). The animals were ultimately sacrificed and their right cochlea and posterior crista ampullaris were removed, processed, and sectioned. The specimens were analyzed for inner hair cell (IHC) and outer hair cell (OHC) loss and vestibular supporting and sensory hair cell nuclei per micrometer of vestibular epithelium. RESULTS: The sound-conditioned group (A) had no loss of cochlear hair cells. The gerbils treated with gentamicin only (B) had a 34% decrease of OHCs and 49% decrease of IHCs. The sound-conditioned plus gentamicin-treated group (C) had a 5.5% decrease in OHCs and 12% decrease in IHCs. There were no significant differences with regards to supporting cell nuclei within the posterior crista across all groups. When compared to group A, the gerbils in groups B and C did have a 23 to 42% decrease in the number of sensory cell nuclei per micrometer of vestibular epithelium. CONCLUSIONS: Sound conditioning does appear to attenuate the effects of gentamicin in the cochlea, although not significantly altering its vestibulotoxicity. An upregulation of cochlear-specific antioxidants is believed to be an important factor. As we had a small sample size, we can only note trends in the data, but future studies with more animals and measurements of antioxidant levels after sound conditioning would be useful to quantify this effect and determine if it can be exploited clinically. Laryngoscope, 2009.

Direct round window application of gentamicin with varying delivery vehicles: a comparison of ototoxicity.

OBJECTIVE: To evaluate patterns of ototoxic damage sustained from gentamicin applied directly to the round window in varying delivery vehicles. SETTING: The search for a reliable method of drug delivery to the inner ear continues. Vehicles such as Gelfoam, hyaluronic acid, and fibrin may allow for a more reproducible pattern of ototoxic damage. STUDY DESIGN: Histological evaluation of vestibular and cochlear damage was performed on Mongolian gerbils after a known dosage of gentamicin in different delivery vehicles. RESULTS: Variable ototoxic damage was caused by Gelfoam and fibrin-based vehicles. No ototoxic damage was found in the Healon vehicle. The vehicle of fibrin and Gelfoam combined resulted in severe damage. There was no evidence of selective cochlear or vestibular ototoxicity in any of the vehicles tested. CONCLUSIONS AND SIGNIFICANCE: The fibrin/Gelfoam vehicle was the only delivery system to produce reliable damage. Ototoxic damage depended on the vehicle. We found no evidence for selective vestibular ototoxicity with gentamicin.