skip to main content

SciTech ConnectSciTech Connect

Title: Ototoxicity of paclitaxel in rat cochlear organotypic cultures

Paclitaxel (taxol) is a widely used antineoplastic drug employed alone or in combination to treat many forms of cancer. Paclitaxel blocks microtubule depolymerization thereby stabilizing microtubules and suppressing cell proliferation and other cellular processes. Previous reports indicate that paclitaxel can cause mild to moderate sensorineural hearing loss and some histopathologic changes in the mouse cochlea; however, damage to the neurons and the underlying cell death mechanisms are poorly understood. To evaluate the ototoxicity of paclitaxel in more detail, cochlear organotypic cultures from postnatal day 3 rats were treated with paclitaxel for 24 or 48 h with doses ranging from 1 to 30 μM. No obvious histopathologies were observed after 24 h treatment with any of the paclitaxel doses employed, but with 48 h treatment, paclitaxel damaged cochlear hair cells in a dose-dependent manner and also damaged auditory nerve fibers and spiral ganglion neurons (SGN) near the base of the cochlea. TUNEL labeling was negative in the organ of Corti, but positive in SGN with karyorrhexis 48 h after 30 μM paclitaxel treatment. In addition, caspase-6, caspase-8 and caspase-9 labeling was present in SGN treated with 30 μM paclitaxel for 48 h. These results suggest that caspase-dependent apoptotic pathways are involvedmore » in paclitaxel-induced damage of SGN, but not hair cells in cochlea. - Highlights: • Paclitaxel was toxic to cochlear hair cells and spiral ganglion neurons. • Paclitaxel-induced spiral ganglion degeneration was apoptotic. • Paclitaxel activated caspase-6, -8 and -8 in spiral ganglion neurons.« less
Authors:
 [1] ;  [2] ; ;  [3] ;  [1] ;  [3] ;  [4]
  1. Shanghai University of Traditional Chinese Medicine, Shanghai 201203 (China)
  2. (United States)
  3. Center for Hearing and Deafness, University at Buffalo, NY 14214 (United States)
  4. Department of Pharmacology and Toxicology, University at Buffalo, NY 14214 (United States)
Publication Date:
OSTI Identifier:
22439899
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 280; Journal Issue: 3; Other Information: Copyright (c) 2014 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ANTINEOPLASTIC DRUGS; APOPTOSIS; CELL PROLIFERATION; DAMAGE; DEPOLYMERIZATION; FIBERS; GANGLIONS; HAIR; MICE; MICROTUBULES; NEOPLASMS; NERVE CELLS; RATS; TOXICITY