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 taxot intraperitoneatly. 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 taxot. No correlation was observed between the dose given and the degree of hearing loss. The sections from the control group showed no histopathologic abnormalities white 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. Conclusion: 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 salisytate and interferon alpha 2a ototoxicity which are thought to be reversible. There was no sensory cell loss. The hearing toss begins with doses less than or equal to 20 mg/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. (c) 2005 Elsevier Ireland Ltd. All rights reserved.