Brimonidine Protects Auditory Hair Cells from in vitro-Induced Toxicity of Gentamicin

Audiol Neurootol. 2017;22(3):125-134. doi: 10.1159/000479218. Epub 2017 Sep 9.

Abstract

Brimonidine, an alpha-2 adrenergic receptor (α2-AR) agonist, has neuroprotective effects in the visual system and in spiral ganglion neurons. Auditory hair cells (HCs) express all 3 α2-AR subtypes, but their roles in HCs remain unknown. This study investigated the effects of brimonidine on auditory HCs that were also exposed to gentamicin, which is toxic to HCs. Organ of Corti explants were exposed to gentamicin in the presence or absence of brimonidine, and the α2-AR protein expression levels and Erk1/2 and Akt phosphorylation levels were determined. Brimonidine had a protective effect on auditory HCs against gentamicin-induced toxicity that was blocked by yohimbine. This suggested that the protective effect of brimonidine on HCs was mediated by the α2-AR. None of the treatments altered α2-AR protein expression levels, and brimonidine did not significantly change the activation levels of the Erk1/2 and Akt proteins. These observations indicated that brimonidine, acting directly via α2-AR, protects HCs from gentamicin-induced toxicity. Therefore, brimonidine shows potential for preventing or treating sensorineural hearing loss.

Keywords: Brimonidine; Gentamicin; Hair cells; Organ of Corti; Toxicity.

MeSH terms

  • Adrenergic alpha-2 Receptor Agonists / pharmacology*
  • Animals
  • Brimonidine Tartrate / pharmacology*
  • Gentamicins / toxicity*
  • Hair Cells, Auditory / drug effects*
  • Hair Cells, Auditory / metabolism
  • MAP Kinase Signaling System / drug effects
  • Neuroprotective Agents / pharmacology*
  • Organ of Corti / drug effects
  • Organ of Corti / metabolism
  • Phosphorylation / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism
  • Rats
  • Rats, Wistar
  • Receptors, Adrenergic, alpha-2 / metabolism

Substances

  • Adrenergic alpha-2 Receptor Agonists
  • Gentamicins
  • Neuroprotective Agents
  • Receptors, Adrenergic, alpha-2
  • Brimonidine Tartrate
  • Proto-Oncogene Proteins c-akt