Protective role of edaravone against neomycin-induced ototoxicity in zebrafish

J Appl Toxicol. 2014 May;34(5):554-61. doi: 10.1002/jat.2964.

Abstract

Aminoglycosides such as neomycin are one of the most commonly prescribed types of antibiotics worldwide. However, these drugs appear to generate free radicals within the inner ear, which can result in permanent hearing loss. We evaluated the effects of edaravone, a neuroprotective agent, on neomycin-induced ototoxicity in transgenic zebrafish. The 5-day post fertilization (dpf) zebrafish larvae were exposed to 125 μM neomycin and various concentrations of edaravone for 1 h. Hair cell survival was calculated as average numbers of the hair cells in the control group, which was not exposed to neomycin. Ultrastructural changes were evaluated using a scanning electron microscope (SEM) and transmission electron microscope (TEM). Edaravone protected against neomycin-induced hair cell loss in the neuromasts (1000 μM: 11.6 ± 1.1 cells, neomycin only: 5.5 ± 0.5 cells; n = 10, P<0.05) and decreased the TUNEL reaction for detecting apoptosis. In ultrastructural analysis, structures of mitochondria and hair cells within neuromasts were preserved in zebrafish exposed to 125 μM neomycin and 1000 μM edaravone for 1 h. Edaravone protected against neomycin-induced hair cell loss by preventing apoptosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Genetically Modified
  • Antipyrine / analogs & derivatives*
  • Antipyrine / pharmacology
  • Apoptosis / drug effects
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Edaravone
  • Embryo, Nonmammalian / drug effects
  • Embryo, Nonmammalian / ultrastructure
  • Hair Cells, Auditory / drug effects*
  • Hair Cells, Auditory / ultrastructure
  • In Situ Nick-End Labeling
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Microscopy, Electron, Transmission
  • Mitochondria / drug effects
  • Mitochondria / ultrastructure
  • Neomycin / toxicity*
  • Neuroprotective Agents / pharmacology*
  • Zebrafish* / embryology
  • Zebrafish* / genetics

Substances

  • Neuroprotective Agents
  • Neomycin
  • Edaravone
  • Antipyrine