Carbaryl-induced ototoxicity in rat postnatal cochlear organotypic cultures.

Details

• Personal Author:
  Ding D ; Prakash Krishnan Muthaiah V ; Roth JA ; Salvi R
• Description:
  Carbaryl, a widely used carbamate-based insecticide, is a potent anticholinesterase known to induce delayed neurotoxicity following chronic exposure. However, its potential toxic effects on the cochlea, the sensory organ for hearing that contains cholinergic efferent neurons and acetylcholine receptors on the hair cells (HC) and spiral ganglion neurons has heretofore not been evaluated. To assess ototoxic potential of carbaryl, cochlear organotypic cultures from postnatal day 3 rats were treated with doses of carbaryl ranging from 50 to 500 µM for 48 h up to 96 h. Carbaryl damaged both the sensory HC and spiral ganglion neurons in a dose- and duration-dependent manner. HC and neuronal damage was observed at carbaryl concentrations as low as 50 µM after 96-h treatment and 100 µM after 48-h treatment. Hair cell was greatest in the high frequency basal region of the cochlea and progressively decreased towards the apex consistent with the majority of ototoxic drugs. In contrast, damage to the spiral ganglion neurons was of similar magnitude in the basal and apical regions of the cochlea. Carbaryl damage was characterized by soma shrinkage, nuclear condensation and fragmentation, and blebbing, morphological features of programmed cell death. Carbaryl upregulated the expression of executioner caspase-3 in HC and spiral ganglion neurons indicating that cellular damage occurred primarily by caspase-mediated apoptosis. These results suggest that chronic exposure to carbaryl and other carbamate anticholinesterases may be ototoxic. [Description provided by NIOSH]
• Subjects:
  Animals Hearing Loss Hearing Loss, Noise-Induced Insecticides Nervous System Nervous System Diseases Occupational Health Safety
• Keywords:
  Author Keywords: Acetylcholinesterase; Carbaryl; Caspase-3; Hair Cells; Hearing Loss; Spiral Ganglion Neurons Neurotoxicity; Carbaryl; Insecticides; Ototoxicity; Neurotoxic Effects; Neurological Disorders; Hearing Loss; Animal Studies;
• ISSN:
  1520-4081
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  Illinois ; New York ; OSHA Region 2 ; OSHA Region 5
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Volume:
  32
• Issue:
  3
• NIOSHTIC Number:
  nn:20069173
• Citation:
  Environ Toxicol 2017 Mar; 32(3):956-969
• Contact Point Address:
  Jerome A. Roth, Department of Pharmacology and Toxicology, University at Buffalo, Buffalo, New York, 14214
• Email:
  jroth@buffalo.edu
• CAS Registry Number:
  Carbaryl (CAS RN 63-25-2)
• Federal Fiscal Year:
  2017
• Performing Organization:
  University of Illinois at Chicago
• Peer Reviewed:
  True
• Start Date:
  20120701
• Source Full Name:
  Environmental Toxicology
• End Date:
  20140630
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:7dc847c09aedf140bc731323e8446b4703641ae07d6ad9e7b7238120dab30b8f7dcaa9b938d34d035f87873a0fe7fec262d5d13dcaf290925445e82b6de3b57d
• Download URL:
  https://stacks.cdc.gov/view/cdc/248308/cdc_248308_DS1.pdf
• File Type:
  [PDF - 168.02 KB ]