Direct drug application to the round window: A comparative study of ototoxicity in rats
This article was presented at the 2008 AAO-HNSF Annual Meeting & OTO EXPO, Chicago, IL, September 21-24, 2008.
Received 24 April 2009; received in revised form 2 July 2009; accepted 28 July 2009.
Abstract
Objective
To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window.
Study Design
Basic, randomized, nonblind experimental study.
Setting
Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies.
Subjects and Methods
Four experimental groups of six Wistar rats with different methods of drug administration were used: (1) injection of subcutaneous kanamycin (400 mg/kg) and intravenous furosemide (100 mg/kg); (2) local application of a sponge soaked in saline close to the round window; (3) animals for which the sponge was soaked in a solution containing kanamycin (200 mg/mL) and furosemide (50 mg/mL); and (4) sham-operated rats. The tympanic bulla was exposed using a ventral approach, and a bullostomy was performed to visualize the round window membrane. Cochlear function was assessed by measuring the auditory brainstem response, and hearing thresholds in response to click and tone burst stimuli were determined as peak and interpeak latencies. At the end of the study, cochlear histology was analyzed.
Results
Systemic administration of kanamycin and furosemide induced profound hearing loss and severe hair cell damage. Local delivery of these ototoxic drugs caused comparable damage but avoided the systemic side effects of the drug. Sham-operated and saline control animals did not experience functional alterations.
Conclusion
Situating a sponge soaked in kanamycin and furosemide on the round window membrane through the ventral approach is a reliable method to provoke local ototoxicity in rats.
aInstituto de Investigaciones Biomédicas ‘Alberto Sols’, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain
bCIBERER (Centro de Investigación Biomédica en Red de Enfermedades Raras) ISC III, Unit 761, Madrid, Spain
cServicio de Otorrinolaringología, Hospital Universitario Príncipe de Asturias, Universidad de Alcalá, Madrid, Spain
Corresponding author: Teresa Rivera, MD, PhD, Servicio de Otorrinolaringología, Hospital Universitario Príncipe de Asturias, Carretera de Alcalá-Meco s/n, Alcalá de Henares, 28805 Madrid, Spain
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
ABSTRACT