Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells.
OBJECTIVE
Test the ability of glutathione monoethyl ester (GSH(e)) to protect auditory hair cells against the ototoxic effects of 4-hydroxy-2,3-nonenal (HNE).


METHODS
Organ of Corti explants were either untreated or treated with one of a series of four concentrations of GSH(e) for one day, then exposed to HNE. Counts of FITC-phalloidin-labeled hair cells determined both HNE ototoxicity and GSH(e) otoprotection.


RESULTS
HNE was toxic to hair cells at physiologically relevant levels, eg, 400 muM, and GSH(e) provided a significant level of protection against HNE ototoxicity (P < 0.05) at all levels tested, ie, 1.16 to 9.3 mM.


CONCLUSIONS
GSH(e) protects auditory hair cells from damage and loss initiated by a naturally occurring ototoxic molecule, ie, HNE (a by-product of oxidative stress).


CONCLUSIONS
Treatment with GSH(e) may be an effective therapy to protect the cochlea against the adverse effects of traumas (eg, electrode insertion) that generate oxidative stress.
Ruiz
Jose W
JW
University of Miami Ear Institute, Department of Otolaryngology, University of Miami, Leonard M. Miller School of Medicine, Miami, Florida, USA.
Guzman
Jose
J
Polak
Marek
M
Eshraghi
Adrien A
AA
Balkany
Thomas J
TJ
Van De Water
Thomas R
TR
D000447:Aldehydes / Q000633:toxicity*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000031:analogs & derivatives* / Q000494:pharmacology; D006198:Hair Cells, Auditory / Q000187:drug effects*; D066298:In Vitro Techniques; D051381:Rats; D017208:Rats, Wistar
D000447:Aldehydes; C042431:S-ethyl glutathione; D005978:Glutathione; C027576:4-hydroxy-2-nonenal