Cobalt-induced ototoxicity in rat postnatal cochlear organotypic cultures

Details

• Personal Author:
  Ding D ; Li P ; Roth JA ; Salvi R
• Description:
  Cobalt (Co) is a required divalent metal used in the production of metal alloys, batteries, and pigments and is a component of vitamin B12. Excessive uptake of Co is neurotoxic causing temporary or permanent hearing loss; however, its ototoxic effects on the sensory hair cells, neurons, and support cells in the cochlea are poorly understood. Accordingly, we treated postnatal day 3 rat cochlear organotypic cultures with various doses and durations of CoCl2 and quantified the damage to the hair cells, peripheral auditory nerve fibers, and spiral ganglion neurons (SGN). Five-day treatment with 250 µM CoCl2 caused extensive damage to hair cells and neurons which increased with dose and treatment duration. CoCl2 caused greater damage to outer hair cells than inner hair cells; damage was greatest in the base of the cochlea and decreased towards the base. CoCl2 increased expression of superoxide radical in hair cells and SGNs and SGN loss was characterized by nuclear condensation and fragmentation, morphological features of apoptosis. CoCl2 treatment increased the expression of caspase-3 indicative of caspase-mediated programmed cell death. These results identify hair cells and spiral ganglion neurons as the main targets of Co ototoxicity in vitro and implicate the superoxide radical as a trigger of caspase-mediated ototoxicity. [Description provided by NIOSH]
• Subjects:
  Animals Hearing Kidney Diseases Laboratories Metals Nervous System Occupational Health Safety Urogenital Diseases Urogenital System
• Keywords:
  Acoustic Neurons Apoptosis Auditory-system Author Keywords: Cobalt Cell-function Cellular-function Cochlea Hair Cells Laboratory-animals Metal-compounds Metallic-compounds Nephrotoxins Neurotoxins Ototoxicity

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• ISSN:
  1029-8428
• 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
• Pages in Document:
  209-221
• Volume:
  28
• Issue:
  3
• NIOSHTIC Number:
  nn:20047453
• Citation:
  Neurotox Res 2015 Oct; 28(3):209-221
• Contact Point Address:
  Jerome A. Roth, Department of Pharmacology and Toxicology, University at Buffalo, 11 Cary Hall, Buffalo, NY 14214, USA
• CAS Registry Number:
  Cobalt (CAS RN 7440-48-4) ; Cobalt chloride (CoCl2) (CAS RN 7646-79-9)
• Federal Fiscal Year:
  2016
• NORA Priority Area:
  Manufacturing
• Performing Organization:
  State University of New York - Buffalo
• Peer Reviewed:
  True
• Start Date:
  20120901
• Source Full Name:
  Neurotoxicity Research
• End Date:
  20170831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:ba193ee5c5398eee8eaceecbb2a59953b50a661a0f8173a134a8129deb760ccc0638858919c386eb2f0673cba7c1615fabc271770b955ea63b76f1e51941094c
• Download URL:
  https://stacks.cdc.gov/view/cdc/202512/cdc_202512_DS1.pdf
• File Type:
  [PDF - 3.09 MB ]