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, iNOS 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 microM). 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 microM 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.
Corbacella
Elisa
E
Department of Audiology, University of Ferrara, 44100 Ferrara, Italy.
Lanzoni
Irene
I
Ding
Dalian
D
Previati
Maurizio
M
Salvi
Richard
R
D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D000900:Anti-Bacterial Agents / Q000494:pharmacology / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D053453:Caspase 9; D061945:Caspase Inhibitors; D020169:Caspases / Q000502:physiology; D003051:Cochlea / Q000187:drug effects / Q000473:pathology; D045304:Cytochromes c / Q000037:antagonists & inhibitors / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005839:Gentamicins / Q000633:toxicity*; D006198:Hair Cells, Auditory / Q000187:drug effects*; D034381:Hearing Loss / Q000139:chemically induced; D008911:Minocycline / Q000494:pharmacology*; D009924:Organ Culture Techniques; D051381:Rats
D000900:Anti-Bacterial Agents; D061945:Caspase Inhibitors; D005839:Gentamicins; D045304:Cytochromes c; C506435:Casp9 protein, rat; D053453:Caspase 9; D020169:Caspases; D008911:Minocycline