Investigation of ototoxic effects of Taxol on a mice model.
ABSTRACT To investigate the effects of taxol on the inner ear in a mice model.
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.
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.
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.
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ABSTRACT: Neuropathic pain as a symptom of sensory nerve damage is a frequent side effect of chemotherapy. The most common behavioral observation in animal models of chemotherapy induced polyneuropathy is the development of mechanical allodynia, which is quantified with von Frey filaments. The data from one study, however, cannot be easily compared with other studies owing to influences of environmental factors, inter-rater variability and differences in test paradigms. To overcome these limitations, automated quantitative gait analysis was proposed as an alternative, but its usefulness for assessing animals suffering from polyneuropathy has remained unclear. In the present study, we used a novel mouse model of paclitaxel induced polyneuropathy to compare results from electrophysiology and the von Frey method to gait alterations measured with the Catwalk test. To mimic recently improved clinical treatment strategies of gynecological malignancies, we established a mouse model of dose-dense paclitaxel therapy on the common C57Bl/6 background. In this model paclitaxel treated animals developed mechanical allodynia as well as reduced caudal sensory nerve action potential amplitudes indicative of a sensory polyneuropathy. Gait analysis with the Catwalk method detected distinct alterations of gait parameters in animals suffering from sensory neuropathy, revealing a minimized contact of the hind paws with the floor. Treatment of mechanical allodynia with gabapentin improved altered dynamic gait parameters. This study establishes a novel mouse model for investigating the side effects of dose-dense paclitaxel therapy and underlines the usefulness of automated gait analysis as an additional easy-to-use objective test for evaluating painful sensory polyneuropathy.PLoS ONE 01/2013; 8(10):e76772. · 3.73 Impact Factor