Oxidative Stress Pathways in the Potentiation of Noise-Induced Hearing Loss by Acrylonitrile

Details

• Personal Author:
  Fechter L ; Fulton S ; Gearhart C ; Nelson-Miller A ; Pouyatos B
• Description:
  We hypothesize that the disruption of antioxidant defenses is a key mechanism whereby chemical contaminants can potentiate noise-induced hearing loss (NIHL). This hypothesis was tested using acrylonitrile (ACN), a widely used industrial chemical whose metabolism is associated with glutathione (GSH) depletion and cyanide (CN) generation. CN, in turn, can inhibit Cu/Zn superoxide dismutase (SOD). We have shown previously that ACN potentiates NIHL, even with noise exposure approaching permissible occupational levels. However, the relative involvement of GSH depletion and/or CN production in this potentiation is still unknown. In this study, we altered these metabolic pathways pharmacologically in order to further delineate the role of specific antioxidants in the protection of the cochlea. We investigated the effects of sodium thiosulfate (STS), a CN inhibitor, 4-methylpyrazole (4MP), a drug that blocks CN generation by competing with CYP2E1, and l-N-acetylcysteine (l-NAC), a pro-GSH drug, in order to distinguish between GSH depletion and CN production as the mechanism responsible for potentiation of NIHL by ACN. Long-Evans rats were exposed to an octave-band noise (97 dB SPL, 4h/day, 5 days) and ACN (50 mg/kg). Separate pre-treatments with STS (150 mg/kg), 4MP (100 mg/kg) and l-NAC (4 x 400 mg/kg) all dramatically reduced blood CN levels, but only l-NAC significantly protected GSH levels in both the liver and the cochlea. Concurrently, only l-NAC treatment decreased the auditory loss and hair cell loss resulting from ACN + noise, suggesting that GSH is involved in the protection of the cochlea against reactive oxygen species generated by moderate noise levels. On the other hand, CN does not seem to be involved in this potentiation. [Description provided by NIOSH]
• Subjects:
  Animals Chemistry Epidemiology Hearing Loss Hearing Loss, Noise-Induced Laboratories Noise Noise, Occupational Occupational Exposure Occupational Health Safety

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• Keywords:
  Animal Studies Chemical Analysis Chemical Composition Chemical Properties Hearing Loss Laboratory Animals Models Noise Control Noise Exposure Noise Induced Hearing Loss Occupational Hazards

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• ISSN:
  0378-5955
• Document Type:
  Text
• Funding:
  Grant
• Genre:
  Journal Article
• Place as Subject:
  California ; OSHA Region 9
• CIO:
  National Institute for Occupational Safety and Health (NIOSH)
• Topic:
  Workplace Safety & Health
• Location:
  North America
• Pages in Document:
  61-74
• Volume:
  224
• Issue:
  1
• NIOSHTIC Number:
  nn:20031887
• Citation:
  Hear Res 2007 Feb; 224(1-2):61-74
• Contact Point Address:
  Benoît Pouyatos, Jerry Pettis Memorial Veterans Medical Center, Department of Veterans Affairs Medical Center, 11201 Benton Street, Loma Linda, CA 92357
• Email:
  benoit.pouyatos@med.va.gov
• CAS Registry Number:
  Acrylonitrile (CAS RN 107-13-1)
• Federal Fiscal Year:
  2007
• NORA Priority Area:
  Disease and Injury: Hearing Loss
• Performing Organization:
  University of Oklahoma, Health Sciences Center, Oklahoma Center for Toxicology, Oklahoma City, Oklahoma
• Peer Reviewed:
  True
• Start Date:
  19970901
• Source Full Name:
  Hearing Research
• End Date:
  20000831
• Collection(s):
  National Institute for Occupational Safety and Health
• Main Document Checksum:
  urn:sha-512:221f86894ad6f7edb8dea2917896f636b360b9a59d536fc71c7f95403c59f21cfdaa4525b7241b9dde5966ebc273c008364f430cf7cdcbf40771a74b501be926
• Download URL:
  https://stacks.cdc.gov/view/cdc/186001/cdc_186001_DS1.pdf
• File Type:
  [PDF - 2.15 MB ]