Investigation of ototoxic effects of Taxol on a mice model
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.
Available from: PubMed Central
- "Two different sets of experiments were performed: In the initial trial, we assigned 15 animals to the treatment and 10 animals to the control group, as previous studies reported a mortality of 25 to 50% for 20 mg/kg body weight (BW) paclitaxel i.p. in mice . In the second experiment, animals were treated with gabapentin after induction of neuropathy with paclitaxel. "
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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.
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ABSTRACT: The present study was undertaken to determine the histopathological and quantitative effects of the antineoplastic agent, taxol, on the liver. The protective effects of the strong antioxidant, beta-1,3-D-glucan, against liver damage induced by taxol were also investigated. Mice were divided into four main treatment groups: control, taxol, beta-1,3-D-glucan, and taxol+beta-1,3-D-glucan. Each group was further subdivided into six subgroups, according to time of sacrifice (6, 12, 24, and 48 hours and 7 and 14 days). After the experiments, quantitative and histopathological changes in liver were examined by light microscopy and modern stereological systems. Stereological results indicated that the portal triad area of the taxol group was significantly reduced, compared to the controls at 12 hours, whereas in the taxol plus beta-glucan and beta-glucan groups, the means were similar to those of the controls. There was no statistically significant difference in the numerical density of hepatocytes with time between the control and other groups. The histopathological results indicated an increased, time-dependent degeneration and necrosis of the liver tissues in mice in the taxol group. Regenerative changes in livers of mice in the taxol plus beta-glucan group were observed, when compared with those of the taxol group. Stereological and histopathological results suggest that beta-glucan may reduce taxol-induced hepatic damage by blocking the change in the portal area and suppressing processes leading to necrosis.
Available from: John W M Yuen
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