PUBLICATION

Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity

Authors
Davis, S.N., Wu, P., Camci, E.D., Simon, J.A., Rubel, E.W., Raible, D.W.
ID
ZDB-PUB-200810-35
Date
2020
Source
Hearing Research   395: 108019 (Journal)
Registered Authors
Keywords
Anti-malarial, Hearing loss, Ototoxicity, Vestibular loss
MeSH Terms
  • Animals
  • Antiviral Agents/toxicity
  • Cell Survival/drug effects*
  • Cells, Cultured
  • Chloroquine/analogs & derivatives*
  • Chloroquine/toxicity
  • Hair Cells, Auditory/cytology
  • Hair Cells, Auditory/drug effects*
  • Hydroxychloroquine/toxicity*
  • Larva/drug effects
  • Lateral Line System/drug effects*
  • Mice
  • Models, Animal
  • Ototoxicity
  • Zebrafish
PubMed
32768772 Full text @ Hear. Res.
Abstract
Hearing and balance deficits have been reported during and following treatment with the antimalarial drug chloroquine. However, experimental work examining the direct actions of chloroquine on mechanoreceptive hair cells in common experimental models is lacking. This study examines the effects of chloroquine on hair cells using two common experimental models: the zebrafish lateral line and neonatal mouse cochlear cultures. Zebrafish larvae were exposed to varying concentrations of chloroquine phosphate or hydroxychloroquine for 1 h or 24 h, and hair cells assessed by antibody staining. A significant, dose-dependent reduction in the number of surviving hair cells was seen across conditions for both exposure periods. Hydroxychloroquine showed similar toxicity. In mouse cochlear cultures, chloroquine damage was specific to outer hair cells in tissue from the cochlear basal turn, consistent with susceptibility to other ototoxic agents. These findings suggest a need for future studies employing hearing and balance monitoring during exposure to chloroquine and related compounds, particularly with interest in these compounds as therapeutics against viral infections including coronavirus.
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Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping