Identifying targets to prevent aminoglycoside ototoxicity

Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in ou...

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Bibliographic Details
Published inMolecular and cellular neuroscience Vol. 120; p. 103722
Main Authors Kim, Jinkyung, Hemachandran, Sriram, Cheng, Alan G., Ricci, Anthony J.
Format Journal Article
LanguageEnglish
Published United States Elsevier Inc 01.05.2022
Subjects
Aminoglycoside
Aminoglycosides - toxicity
Anti-Bacterial Agents - adverse effects
Cochlea
Hair cell
Humans
Ototoxicity
ST
OoC
SV
GTTR
AG(s)
OHC(s)
TRP
HC(s)
Aminoglycoside
Cochlea
BLB
Hair cell
SM
IHC(s)
MET
ATP
Ototoxicity
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Summary:Aminoglycosides are potent antibiotics that are commonly prescribed worldwide. Their use carries significant risks of ototoxicity by directly causing inner ear hair cell degeneration. Despite their ototoxic side effects, there are currently no approved antidotes. Here we review recent advances in our understanding of aminoglycoside ototoxicity, mechanisms of drug transport, and promising sites for intervention to prevent ototoxicity. •Aminoglycosides cause irreversible hearing loss by inducing cochlear hair cell death.•Diuretics and sepsis potentiate aminoglycoside uptake into the cochlea and ototoxicity.•Aminoglycoside enters hair cells via mechanotransducer channels.•Blockers of mechanotransducer channels or designer aminoglycosides prevent hair cell degeneration.
Bibliography:equal contribution
ISSN:1044-7431
1095-9327
DOI:10.1016/j.mcn.2022.103722