Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures

Minocycline, a second-generation tetracycline antibiotic used against gram-negative and gram-positive bacteria, protects against a wide range of neurodegenerative disorders by inhibiting caspases, NOS and the release of cytochrome c. Since aminoglycoside antibiotics damage sensory hair cells in the inner ear by activating caspase-mediated cell death pathways, we hypothesized that minocycline would protect against gentamicin (GM) ototoxicity. To test this hypothesis, postnatal day 3 (P3) rat, cochlear organotypic cultures were treated with GM alone or in combination with minocycline (10-500 muM). Treatment with GM induced a dose-dependent loss of outer hair cells (OHC) and inner hair cells (IHC). Addition of minocycline to the GM-treated cultures greatly reduced the amount of GM-induced hair cell damage in P3 cochlear cultures. The greatest protection was achieved with 100 muM of minocycline. Application of minocycline alone had no adverse effects on hair cell survival. The advantage of this combination therapy is that minocycline prevents GM-induced hair cell loss while helping to suppress the bacterial infection. (C) 2004 Published by Elsevier B.V.