Calpain and caspase inhibitors protect vestibular sensory cells from gentamicin ototoxicity.
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.
Shimizu
Akira
A
Department of Otolaryngology, Tokyo Medical University, Tokyo, Japan. chachi@v006.vaio.ne.jp
Takumida
Masaya
M
Anniko
Matti
M
Suzuki
Mamoru
M
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
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