Glutathione ester protects against hydroxynonenal-induced loss of auditory hair cells

Abstract

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). 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. 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. 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). 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.