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

Otolaryngol Head Neck Surg. 2006 Nov;135(5):792-7. doi: 10.1016/j.otohns.2006.05.031.

Abstract

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).

Study design and setting: 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.

Conclusion: 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).

Significance: 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.

MeSH terms

  • Aldehydes / toxicity*
  • Animals
  • Dose-Response Relationship, Drug
  • Glutathione / analogs & derivatives*
  • Glutathione / pharmacology
  • Hair Cells, Auditory / drug effects*
  • In Vitro Techniques
  • Rats
  • Rats, Wistar

Substances

  • Aldehydes
  • S-ethyl glutathione
  • Glutathione
  • 4-hydroxy-2-nonenal