Chloroquine kills hair cells in zebrafish lateral line and murine cochlear cultures: Implications for ototoxicity
| Autor: | Patricia Wu, David W. Raible, Samantha N. Davis, Edwin W. Rubel, Julian A. Simon, Esra D. Camci |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Cell Survival Hearing loss Vestibular loss Pharmacology medicine.disease_cause Antiviral Agents Article Mice Basal (phylogenetics) 03 medical and health sciences 0302 clinical medicine Ototoxicity Chloroquine Hair Cells Auditory otorhinolaryngologic diseases Animals Medicine Zebrafish Cells Cultured 030304 developmental biology Coronavirus 0303 health sciences biology business.industry Hydroxychloroquine medicine.disease biology.organism_classification Chloroquine Phosphate Sensory Systems Lateral Line System 3. Good health 030104 developmental biology Larva Models Animal Toxicity Anti-malarial sense organs medicine.symptom business 030217 neurology & neurosurgery medicine.drug |
| Zdroj: | Hearing Research |
| ISSN: | 0378-5955 |
| DOI: | 10.1016/j.heares.2020.108019 |
| Popis: | 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. Highlights • Chloroquine exposure results in rapid, dose-dependent hair cell damage in zebrafish. • Hydroxychloroquine shows similar toxicity to chloroquine. • Chloroquine specifically kills hair cells in mouse neonatal cochlear cultures. • Chloroquine damage is preferential to basal cochlea outer hair cells. |
| Databáze: | OpenAIRE |
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