title: Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin ototoxicity.
abstract: OBJECTIVE
  Apoptosis may play an important role in the mechanism of aminoglycoside ototoxicity. Caspases and calpains are regarded to be important factors in the regulation of cell death in the inner ear. We hypothesized that caspase or calpain inhibitors would protect hair cells from aminoglycoside ototoxicity.
  
  
  METHODS
  In order to test this hypothesis we carried out a pilot study to determine if gentamicin (GM) would induce caspase and calpain immunolabeling in guinea pig hair cells Having confirmed this we carried out the main experiment using guinea pig vestibular organ culture to determine if caspase and calpain would protect the hair cells from GM ototoxicity.
  
  
  RESULTS
  Immunoreactivity for caspase-3 and m-calpain was detected in the vestibular sensory cells and ganglia after GM treatment. Both caspase and calpain inhibitors protected hair cells against gentamicin ototoxicity.
  
  
  CONCLUSIONS
  It is suggested that inhibition of apoptosis is essential in order to block aminoglycoside ototoxicity.
authors.affiliation: Department of Otolaryngology, Tokyo Medical University, Tokyo, Japan. chachi@v006.vaio.ne.jp
authors.forename: Akira
authors.initials: A
authors.lastname: Shimizu
authors.forename: Masaya
authors.initials: M
authors.lastname: Takumida
authors.forename: Matti
authors.initials: M
authors.lastname: Anniko
authors.forename: Mamoru
authors.initials: M
authors.lastname: Suzuki
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D002154:Calpain / Q000037:antagonists & inhibitors*; D061945:Caspase Inhibitors; D002403:Cathepsins / Q000037:antagonists & inhibitors; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D006168:Guinea Pigs; D018069:Hair Cells, Vestibular / Q000187:drug effects*; D007976:Leupeptins / Q000494:pharmacology; D009842:Oligopeptides / Q000494:pharmacology; D009924:Organ Culture Techniques; D010865:Pilot Projects
chemical_list: D000900:Anti-Bacterial Agents; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; D005839:Gentamicins; D007976:Leupeptins; D009842:Oligopeptides; C110772:benzoylcarbonyl-aspartyl-glutamyl-valyl-aspartyl-fluoromethyl ketone; D002403:Cathepsins; D002154:Calpain; C032854:leupeptin