PUBLICATION

Tetrabromobisphenol-A induces apoptotic death of auditory cells and hearing loss

Authors
Park, C., Kim, S.J., Lee, W.K., Moon, S.K., Kwak, S., Choe, S.K., Park, R.
ID
ZDB-PUB-160907-10
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
  • Mechanoreceptors/drug effects
  • Mechanoreceptors/metabolism
  • Reactive Oxygen Species/metabolism
  • Polybrominated Biphenyls/toxicity*
  • Evoked Potentials, Auditory, Brain Stem/drug effects
  • Organ of Corti/drug effects
  • Organ of Corti/metabolism
  • Organ of Corti/physiopathology
  • Rats, Sprague-Dawley
  • Animals
  • Apoptosis/drug effects*
  • Reverse Transcriptase Polymerase Chain Reaction
  • Zebrafish
  • Cell Line
  • Hair Cells, Auditory/drug effects*
  • Hair Cells, Auditory/metabolism
  • Blotting, Western
  • Interleukin-6/genetics
  • Interleukin-6/metabolism
  • Flame Retardants/toxicity
  • Microscopy, Fluorescence
  • Lateral Line System/drug effects
  • Lateral Line System/metabolism
  • Lateral Line System/physiopathology
  • Mice, Inbred ICR
  • Gene Expression/drug effects
  • Free Radical Scavengers/pharmacology
  • Hearing Loss/chemically induced*
  • Hearing Loss/physiopathology
  • Hearing Loss/prevention & control
  • Apoptosis Regulatory Proteins/metabolism
PubMed
27592553 Full text @ Biochem. Biophys. Res. Commun.
CTD
27592553
Abstract
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.
Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping