Hydrogen protects auditory hair cells from cisplatin-induced free radicals

Neurosci Lett. 2014 Sep 5:579:125-9. doi: 10.1016/j.neulet.2014.07.025. Epub 2014 Jul 23.

Abstract

Cisplatin is a widely used chemotherapeutic agent for the treatment of various malignancies. However, its maximum dose is often limited by severe ototoxicity. Cisplatin ototoxicity may require the production of reactive oxygen species (ROS) in the inner ear by activating enzymes specific to the cochlea. Molecular hydrogen was recently established as an antioxidant that selectively reduces ROS, and has been reported to protect the central nervous system, liver, kidney and cochlea from oxidative stress. The purpose of this study was to evaluate the potential of molecular hydrogen to protect cochleae against cisplatin. We cultured mouse cochlear explants in medium containing various concentrations of cisplatin and examined the effects of hydrogen gas dissolved directly into the media. Following 48-h incubation, the presence of intact auditory hair cells was assayed by phalloidin staining. Cisplatin caused hair cell loss in a dose-dependent manner, whereas the addition of hydrogen gas significantly increased the numbers of remaining auditory hair cells. Additionally, hydroxyphenyl fluorescein (HPF) staining of the spiral ganglion showed that formation of hydroxyl radicals was successfully reduced in hydrogen-treated cochleae. These data suggest that molecular hydrogen can protect auditory tissues against cisplatin toxicity, thus providing an additional strategy to protect against drug-induced inner ear damage.

Keywords: Antioxidant; Chemotherapy; Cochlea; Hearing loss; Hydroxyl radical; Reactive oxygen species.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / toxicity*
  • Cell Survival / drug effects
  • Cisplatin / antagonists & inhibitors*
  • Cisplatin / toxicity*
  • Cochlear Diseases / chemically induced
  • Cochlear Diseases / prevention & control
  • Dose-Response Relationship, Drug
  • Free Radicals / toxicity*
  • Gases
  • Hair Cells, Auditory / drug effects*
  • Hydrogen / pharmacology*
  • Mice
  • Mice, Inbred ICR
  • Reactive Oxygen Species / metabolism
  • Spiral Ganglion / drug effects
  • Spiral Ganglion / metabolism

Substances

  • Antineoplastic Agents
  • Free Radicals
  • Gases
  • Reactive Oxygen Species
  • Hydrogen
  • Cisplatin