Cellular mechanisms of aminoglycoside ototoxicity.
OBJECTIVE
To summarize advances in the study of the interaction between sensory hair cells and aminoglycoside antibiotics.


RESULTS
Aminoglycosides enter hair cells through mechanotransduction channels and initiate an active signaling pathway that leads to cell death. Early expression of heat shock proteins can protect hair cells from aminoglycosides, although signaling from surrounding supporting cells appears to promote hair cell death. Studies of certain human deafness mutations have revealed new insights into the role of mitochondria in aminoglycoside ototoxicity.


CONCLUSIONS
The cellular mechanisms of aminoglycoside ototoxicity continue to be an active topic of research and newly developed animal models offer great promise for future advances. Nevertheless, proven clinical methods for the prevention of ototoxic injury are not yet available.
Warchol
Mark E
ME
Department of Otolaryngology, Washington University School of Medicine, St Louis, Missouri 63110, USA. warcholm@ent.wustl.edu
D000617:Aminoglycosides / Q000009:adverse effects*; D000818:Animals; D000900:Anti-Bacterial Agents / Q000009:adverse effects*; D006198:Hair Cells, Auditory / Q000187:drug effects*; D006801:Humans
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents