PUBLICATION
Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle
- Authors
- Ou, H.C., Cunningham, L.L., Francis, S.P., Brandon, C.S., Simon, J.A., Raible, D.W., and Rubel, E.W.
- ID
- ZDB-PUB-090302-24
- Date
- 2009
- Source
- Journal of the Association for Research in Otolaryngology : JARO 10(2): 191-203 (Journal)
- Registered Authors
- Raible, David
- Keywords
- FDA library, zebrafish, hair cell, protection, ototoxicity, aminoglycoside
- MeSH Terms
-
- Animals
- Anti-Bacterial Agents/administration & dosage
- Anti-Bacterial Agents/toxicity
- Cell Survival/drug effects
- Cholinesterase Inhibitors/administration & dosage
- Dose-Response Relationship, Drug
- Drug Evaluation, Preclinical/methods*
- Hair Cells, Auditory/drug effects*
- Lateral Line System/drug effects*
- Male
- Mechanotransduction, Cellular
- Mice
- Neomycin/administration & dosage
- Neomycin/toxicity
- Pharmaceutical Preparations/administration & dosage*
- Saccule and Utricle/drug effects*
- Tacrine/administration & dosage
- United States
- United States Food and Drug Administration
- Zebrafish
- PubMed
- 19241104 Full text @ J. Assoc. Res. Otolaryngol.
Citation
Ou, H.C., Cunningham, L.L., Francis, S.P., Brandon, C.S., Simon, J.A., Raible, D.W., and Rubel, E.W. (2009) Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle. Journal of the Association for Research in Otolaryngology : JARO. 10(2):191-203.
Abstract
The hair cells of the larval zebrafish lateral line provide a useful preparation in which to study hair cell death and to screen for genes and small molecules that modulate hair cell toxicity. We recently reported preliminary results from screening a small-molecule library for compounds that inhibit aminoglycoside-induced hair cell death. To potentially reduce the time required for development of drugs and drug combinations that can be clinically useful, we screened a library of 1,040 FDA-approved drugs and bioactive compounds (NINDS Custom Collection II). Seven compounds that protect against neomycin-induced hair cell death were identified. Four of the seven drugs inhibited aminoglycoside uptake, based on Texas-Red-conjugated gentamicin uptake. The activities of two of the remaining three drugs were evaluated using an in vitro adult mouse utricle preparation. One drug, 9-amino-1,2,3,4-tetrahydroacridine (tacrine) demonstrated conserved protective effects in the mouse utricle. These results demonstrate that the zebrafish lateral line can be used to screen successfully for drugs within a library of FDA-approved drugs and bioactives that inhibit hair cell death in the mammalian inner ear and identify tacrine as a promising protective drug for future studies.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping