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Prevention of gentamicin-induced apoptosis with the mitochondria-targeted antioxidant mitoquinone

Carolyn P Ojano-Dirain1, Patrick J Antonelli

  • 1Department of Otolaryngology, University of Florida College of Medicine, Gainesville, Florida, USA. carolyn.ojano-dirain@ent.ufl.edu

The Laryngoscope
|September 12, 2012
PubMed
Abstract

Insights

Mitoquinone (MitoQ) reduces gentamicin-induced cell death by decreasing apoptosis. This mitochondria-targeted antioxidant does not impact gentamicin

Area of Science:

  • Cell Biology
  • Pharmacology
  • Ototoxicity Research

Background:

  • Aminoglycosides, like gentamicin, can cause hearing loss through ototoxicity.
  • Antioxidants show potential in protecting against aminoglycoside-induced hearing loss.
  • Mitoquinone (MitoQ) is a mitochondria-targeted antioxidant derivative of ubiquinone, designed for enhanced mitochondrial accumulation.

Purpose of the Study:

  • To evaluate if MitoQ can reduce gentamicin-induced apoptosis by measuring caspase-3/7 activity.
  • To assess the impact of MitoQ on the antimicrobial effectiveness of gentamicin.

Main Methods:

  • Prospective, controlled study design.
  • Broth dilution methods were used to determine gentamicin's minimum inhibitory concentrations (MICs) against Staphylococcus aureus, Haemophilus influenzae, and Pseudomonas aeruginosa, with and without MitoQ.
  • Apoptosis was assessed via caspase-3/7 activity in HEI-OC1 cells treated with gentamicin, with or without preincubation with MitoQ, idebenone, or decylTPP.

Main Results:

  • MitoQ did not alter gentamicin MICs for P. aeruginosa and H. influenzae but enhanced MICs for S. aureus.
  • Gentamicin treatment significantly reduced cell viability and increased caspase-3/7 activity, indicating apoptosis.
  • Preincubation with MitoQ significantly attenuated gentamicin-induced apoptosis more effectively than idebenone.

Conclusions:

  • MitoQ effectively reduces gentamicin-induced apoptosis in HEI-OC1 cells.
  • MitoQ does not compromise the antibiotic efficacy of gentamicin.
  • MitoQ shows promise for preventing aminoglycoside-induced ototoxicity.

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