Minocycline prevents gentamicin-induced ototoxicity by inhibiting p38 MAP kinase phosphorylation and caspase 3 activation

X. Wei, L. Zhao, J. Liu, R. C. Dodel, M. R. Farlow, Y. Du

Research output: Contribution to journalArticle

62 Scopus citations

Abstract

Aminoglycosides are commonly used antibiotics that often induce ototoxicity leading to permanent hair cell loss and hearing impairment. We hereby examined whether minocycline protects hair cells from gentamicin-induced hair cell damage. Two millimolar gentamicin significantly induced outer hair cell damage and the addition of minocycline to gentamicin-treated explants significantly increased hair cell survival in a dose-dependent manner. Additionally, we demonstrated that gentamicin induced p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation in these cells and these remarkable changes were blocked by minocycline treatments. Furthermore, we showed that the inhibitor of p38 MAPK or the inhibitor of caspase 3 only partially blocked gentamicin-induced hair cell damage, and the pretreatment of explants with the inhibitor of p38 MAPK and the inhibitor of caspase 3 together exerted a synergic protective effect against gentamicin-induced hair cell damage. Our results suggest that minocycline blocks gentamicin-induced hair cell loss possibly by inhibition of three mechanisms: p38 MAPK phosphorylation, cytochrome c release, and caspase 3 activation. This finding may explain why minocycline has protective activity in a variety of apoptotic models. Therapeutic intervention by using minocycline or related drugs may be a novel means for preventing inner ear injury following the use of aminoglycoside.

Original languageEnglish (US)
Pages (from-to)513-521
Number of pages9
JournalNeuroscience
Volume131
Issue number2
DOIs
StatePublished - Jan 1 2005

Keywords

  • Apoptosis
  • Caspase 3
  • Hair Cell
  • Minocycline
  • Ototoxicity
  • p38 MAP kinase

ASJC Scopus subject areas

  • Neuroscience(all)

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