Some Ototoxic Drugs Destroy Cochlear Support Cells Before Damaging Sensory Hair Cells

Details

• Personal Author:
  Ding D ; Jiang H ; Qi W ; Salvi R ; Xuan W ; Zhang J
• Description:
  A wide variety of ototoxic drugs are capable of damaging the sensory hair cells in the mammalian cochlea resulting in permanent hearing loss. However, the toxic properties of these drugs suggest that some could potentially damage cochlear support cells as well. To test the hypothesis, we treated postnatal day three rat cochlear cultures with toxic doses of gentamicin, cisplatin, mefloquine, and cadmium. Gentamicin primarily destroyed the hair cells and disrupted the intercellular connection with the surrounding support cells. Gentamicin-induced hair cell death was initiated through the caspase-9 intrinsic apoptotic pathway followed by activation of downstream executioner caspase-3. In contrast, cisplatin, mefloquine, and cadmium initially damaged the support cells and only later damaged the hair cells. Support cell death was initiated through the caspase-8 extrinsic apoptotic pathway followed later by downstream activation of caspase-3. Cisplatin, mefloquine, and cadmium significantly reduced the expression of actin and laminin, in the extracellular matrix, leading to significant disarray of the sensory epithelium. [Description provided by NIOSH]
• Subjects:
  Antibodies Ear Environmental Exposure Hearing Loss Hearing Loss, Noise-Induced Laboratories Necrosis Occupational Health Pathology Safety Sense Organs

  More +
• Keywords:
  Apoptosis Auditory Nerve Auditory System Author Keywords: Hair Cells Caspase Cell Damage Cell Death Cellular Effects Chemicals Cochlea Drugs Ears Exposure Assessment Exposure Levels Hearing Loss Laboratory Animals Laboratory Testing Ototoxicity Support Cells Toxic Dose Toxic Effects

  More +
• 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
• Volume:
  37
• Issue:
  3
• NIOSHTIC Number:
  nn:20058472
• Citation:
  Neurotox Res 2020 Mar; 37(3):743-752
• Contact Point Address:
  Richard Salvi, Center for Hearing and Deafness, University at Buffalo, 137 Cary Hall, Buffalo, NY 14214, USA
• Email:
  salvi@buffalo.edu
• CAS Registry Number:
  Cadmium (CAS RN 7440-43-9) ; Cisplatin (CAS RN 15663-27-1) ; Gentamicin (CAS RN 1403-66-3) ; Mefloquine (CAS RN 53230-10-7)
• Federal Fiscal Year:
  2020
• 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-512:7f4200e675e926c681012829efcc5e4e10f203a95d8265a8f07fe7d3498f506a67f0ff25f4bb8fb662e48f2ead58027d2ba0a293a1e824b3864fbf585e03ec8d
• Download URL:
  https://stacks.cdc.gov/view/cdc/221561/cdc_221561_DS1.pdf
• File Type:
  [PDF - 727.80 KB ]