[HTML][HTML] Identification of FDA-Approved Drugs and Bioactives that Protect Hair Cells in the Zebrafish (Danio rerio) Lateral Line and Mouse (Mus musculus) Utricle
HC Ou, LL Cunningham, SP Francis… - Journal of the …, 2009 - Springer
Journal of the Association for Research in Otolaryngology, 2009•Springer
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 …
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 …
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.
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