Direct drug application to the round window: a comparative study of ototoxicity in rats.
OBJECTIVE
To assess the validity of inducing ototoxicity in rats by applying a sponge soaked in kanamycin and furosemide on the round window.


METHODS
Basic, randomized, nonblind experimental study.


METHODS
Animal models of cochlear damage and reliable methods of local drug delivery are fundamental to study hearing loss and to design new therapies.


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.


CONCLUSIONS
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.
Instituto de Investigaciones Biomédicas Alberto Sols, Consejo Superior de Investigaciones Científicas-Universidad Autónoma de Madrid, Madrid, Spain.
Silvia
S
Murillo-Cuesta
Fernando
F
García-Alcántara
Elena
E
Vacas
Jon Alexander
JA
Sistiaga
Guadalupe
G
Camarero
Isabel
I
Varela-Nieto
Teresa
T
Rivera
D000287:Administration, Topical; D000818:Animals; D003051:Cochlea / Q000187:drug effects / Q000473:pathology / Q000502:physiology; D016057:Evoked Potentials, Auditory, Brain Stem; D005665:Furosemide / Q000633:toxicity; D034381:Hearing Loss / Q000139:chemically induced; D007275:Injections, Intravenous; D007279:Injections, Subcutaneous; D007612:Kanamycin / Q000633:toxicity; D008297:Male; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012405:Round Window, Ear / Q000187:drug effects*
D007612:Kanamycin; D005665:Furosemide