Ototoxicity of paclitaxel in rat cochlear organotypic cultures

Details

• Personal Author:
  Ding D ; Dong Y ; Jiang H ; Roth JA ; Salvi R ; Shi J-R
• Description:
  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 24h 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 involved in paclitaxel-induced damage of SGN, but not hair cells in cochlea. [Description provided by NIOSH]
• Subjects:
  Animals Antineoplastic Agents Drug Therapy Hearing Loss Laboratories Neoplasms Occupational Health Safety
• Keywords:
  Antineoplastic-agents Author Keywords: Paclitaxel Cancer Cell-function Cellular-function Cochlea Drug-therapy Drugs Hair Cells Apoptosis Hearing-loss Histopathology Laboratory-animals Ototoxicity Spiral Ganglion Neurons

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• ISSN:
  0041-008X
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  New York ; OSHA Region 2
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  280
• Issue:
  3
• NIOSHTIC Number:
  nn:20045652
• Citation:
  Toxicol Appl Pharmacol 2014 Nov; 280(3):526-533
• Contact Point Address:
  Jerome A. Rothc, Department of Pharmacology and Toxicology, 11 Cary Hall, University at Buffalo, Buffalo, NY 14214
• Email:
  jaroth@buffalo.edu
• Federal Fiscal Year:
  2015
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  State University of New York - Buffalo
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Toxicology and Applied Pharmacology
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:4fdcf6af7d86a0316e4f6ee46f700e210bdc98157aa1f03cdd39c01ab660403e7002145cb06955176049d72cf0bef45ed0722f0c158e40a15e76e189e274a853
• Download URL:
  https://stacks.cdc.gov/view/cdc/200998/cdc_200998_DS1.pdf
• File Type:
  [PDF - 2.28 MB ]