ZFIN ID: ZDB-PUB-160907-10
Tetrabromobisphenol-A induces apoptotic death of auditory cells and hearing loss
Park, C., Kim, S.J., Lee, W.K., Moon, S.K., Kwak, S., Choe, S.K., Park, R.
Date: 2016
Source: Biochemical and Biophysical Research Communications   478(4): 1667-73 (Journal)
Registered Authors: Choe, Seong-Kyu
Keywords: Apoptosis, Hair cells, Hearing loss, TBBPA, Zebrafish neuromast
MeSH Terms:
  • Acetylcysteine/pharmacology
  • Animals
  • Apoptosis/drug effects*
  • Apoptosis Regulatory Proteins/metabolism
  • Blotting, Western
  • Cell Line
  • Evoked Potentials, Auditory, Brain Stem/drug effects
  • Flame Retardants/toxicity
  • Free Radical Scavengers/pharmacology
  • Gene Expression/drug effects
  • Hair Cells, Auditory/drug effects*
  • Hair Cells, Auditory/metabolism
  • Hearing Loss/chemically induced*
  • Hearing Loss/physiopathology
  • Hearing Loss/prevention & control
  • Interleukin-6/genetics
  • Interleukin-6/metabolism
  • Lateral Line System/drug effects
  • Lateral Line System/metabolism
  • Lateral Line System/physiopathology
  • Mechanoreceptors/drug effects
  • Mechanoreceptors/metabolism
  • Mice, Inbred ICR
  • Microscopy, Fluorescence
  • Organ of Corti/drug effects
  • Organ of Corti/metabolism
  • Organ of Corti/physiopathology
  • Polybrominated Biphenyls/toxicity*
  • Rats, Sprague-Dawley
  • Reactive Oxygen Species/metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish
PubMed: 27592553 Full text @ Biochem. Biophys. Res. Commun.
Phenolic tetrabromobisphenol-A (TBBPA) and its derivatives are commonly used flame-retardants, in spite of reported toxic effects including neurotoxicity, immunotoxicity, nephrotoxicity, and hepatotoxicity. However, the effects of TBBPA on ototoxicity have not yet been reported. In this study, we investigated the effect of TBBPA on hearing function in vivo and in vitro. Auditory Brainstem Response (ABR) threshold was markedly increased in mice after oral administration of TBBPA, indicating that TBBPA causes hearing loss. In addition, TBBPA induced the loss of both zebrafish neuromasts and hair cells in the rat cochlea in a dose-dependent manner. Mechanistically, hearing loss is largely attributed to apoptotic cell death, as TBBPA increased the expression of pro-apoptotic genes but decreased the expression of anti-apoptotic genes. We also found that TBBPA induced oxidative stress, and importantly, pretreatment with NAC, an anti-oxidant reagent, reduced TBBPA-induced reactive oxygen species (ROS) generation and partially prevented cell death. Our results show that TBBPA-mediated ROS generation induces ototoxicity and hearing loss. These findings implicate TBBPA as a potential environmental ototoxin by exerting its hazardous effects on the auditory system.