Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus ... View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-02-25

AUTHORS

Henry C. Ou, Lisa L. Cunningham, Shimon P. Francis, Carlene S. Brandon, Julian A. Simon, David W. Raible, Edwin W Rubel

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. More... »

PAGES

191-203

References to SciGraph publications

  • 2003-11-12. Uptake of Gentamicin by Bullfrog Saccular Hair Cells in vitro in JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
  • 2005-01. β-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression in NATURE
  • 2005-07-15. Caspase-independent pathways of hair cell death induced by kanamycin in vivo in CELL DEATH & DIFFERENTIATION
  • 2003-05-06. Neomycin-Induced Hair Cell Death and Rapid Regeneration in the Lateral Line of Zebrafish (Danio rerio) in JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
  • 2008-04-12. Using the Zebrafish Lateral Line to Screen for Ototoxicity in JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY
  • 1992-11. Comparison of the blood-brain barrier and liver penetration of acridine antitumor drugs in CANCER CHEMOTHERAPY AND PHARMACOLOGY
  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1007/s10162-009-0158-y

    DOI

    http://dx.doi.org/10.1007/s10162-009-0158-y

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1031378997

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/19241104


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