Minocycline attenuates gentamicin induced hair cell loss in neonatal cochlear cultures

• Published in: Hearing research Vol. 197; no. 1; pp. 11 - 18
• Main Authors: Corbacella, Elisa, Lanzoni, Irene, Ding, Dalian, Previati, Maurizio, Salvi, Richard
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.11.2004; Elsevier
• Subjects: Analysis of Variance; Animals; Animals, Newborn; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - toxicity; Apoptosis; Apoptosis - drug effects; Biological and medical sciences; Caspase 9; Caspase Inhibitors; Caspases - physiology; Cochlea - drug effects; Cochlea - pathology; Cytochrome c; Cytochromes c - antagonists & inhibitors; Cytochromes c - physiology; Dose-Response Relationship, Drug; Drug toxicity and drugs side effects treatment; Ear, auditive nerve, cochleovestibular tract, facial nerve: diseases, semeiology; Gentamicin; Gentamicins - toxicity; Hair cells; Hair Cells, Auditory - drug effects; Hearing Loss - chemically induced; Medical sciences; Minocycline; Minocycline - pharmacology; Non tumoral diseases; Organ Culture Techniques; Otorhinolaryngology. Stomatology; Ototoxicity; Pharmacology. Drug treatments; Rats; Toxicity: respiratory system, ent, stomatology; Gentamicin; Hair cells; OHC, outer hair cell; GM, gentamicin; Cytochrome c; iNOS, inducible nitric oxide synthetase; MPTP, mitochondrial permeability transition pore; IHC, inner hair cell; Minocycline; SIMP, soluble intermembrane proteins; MAPK, mitogen-activated protein kinase; Ototoxicity; Apoptosis; Rat; Toxicity; Organotypic culture; Inner ear; Organ of hearing; ENT disease; Bacteria; Enzyme; Internal ear disease; Rodentia; Caspase; Neuroprotective agent; Peptidases; Vertebrata; Antibiotic; Mammalia; Cell death; Aminoglycoside; Animal; Cochlea; Inner hair cell; Hydrolases
• ISSN: 0378-5955; 1878-5891
• DOI: 10.1016/j.heares.2004.03.012

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 μM). 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 μM 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.