Investigation of ototoxic effects of Taxol on a mice model.
OBJECTIVE
To investigate the effects of taxol on the inner ear in a mice model.


METHODS
This study was performed on 112 ears of 56 albino Swiss mice. All animals underwent baseline auditory brainstem response (ABR) testing bilaterally and baseline Peak Equivalent Sound Pressure Levels (PESPLs) were obtained. The mice were randomly assigned to seven groups consisting of one control and six study groups. The control group received no medications while the mice in groups 1-6 received 1 x 60, 1 x 20, 2 x 20, 3 x 20, 4 x 20 and 5 x 20 mg/kg taxol intraperitoneally. Control ABR assessments were performed 3 weeks after the last dose. The animals were then sacrificed while still anaesthetised and the bullae (cochleae included) were dissected from their temporal bones. Haematoxylin-eosin and Masson's trichrome stains were used to demonstrate connective tissue, and periodic acid Schiff (PAS) stain was used to highlight epithelial elements.


RESULTS
Significant decreases in the hearing levels were observed in all the groups which received taxol. No correlation was observed between the dose given and the degree of hearing loss. The sections from the control group showed no histopathologic abnormalities while the sections from the study groups demonstrated vacuolisation in the epithelial cells of the spiral limbus, and the stria vascularis, vacuolisation of the fibroblasts and decreasing the number of the fibroblasts in the spiral limbus.


CONCLUSIONS
Taxol causes mild to moderate sensorineural hearing loss in mice. Histopathologically, there were degenerative changes in the cochlea resembling the ones that take place in salisylate and interferon alpha 2a ototoxicity which are thought to be reversible. There was no sensory cell loss. The hearing loss begins with doses less than or equal to 20mg/kg and is not dose dependent after this dose. Hearing monitorisation with audiologic evaluation is strongly recommended before and during the use of the drug in human subjects.
Atas
Ahmet
A
Department of Audiology, Hacettepe University Medical Faculty, Ankara, Turkey.
Agca
Orhan
O
Sarac
Sarp
S
Poyraz
Aylar
A
Akyol
M Umut
MU
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000633:toxicity*; D001309:Auditory Threshold / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D004847:Epithelial Cells / Q000187:drug effects / Q000473:pathology; D005347:Fibroblasts / Q000378:metabolism / Q000473:pathology; D006319:Hearing Loss, Sensorineural / Q000139:chemically induced*; D007274:Injections, Intraperitoneal; D051379:Mice; D023421:Models, Animal; D017239:Paclitaxel / Q000633:toxicity*; D011897:Random Allocation; D014617:Vacuoles / Q000473:pathology
D000972:Antineoplastic Agents, Phytogenic; D017239:Paclitaxel