Neuroprotection of Vestibular Sensory Cells from Gentamicin Ototoxicity Obtained Using Nitric Oxide Synthase Inhibitors, Reactive Oxygen Species Scavengers, Brain-derived Neurotrophic Factors and Calpain Inhibitors

Abstract

Objective--In order to devise a new treatment for inner ear disorders, the efficacy of a nitric oxide synthase inhibitor (L-N^G-nitroarginine methylester [L-NAME]), a radical scavenger (D-methionine), a neurotrophin (brain-derived neurotrophic factor [BDNF]) and a calpain inhibitor (leupeptin) for protection from hair cell damage was investigated. Material and methods--The effects of these drugs on gentamicin-induced production of nitric oxide (NO) and reactive oxygen species (ROS) were studied by means of the fluorescence indicators 4,5-diaminofluorescein diacetate and dihydrotetramethylrosamine. The effect on gentamicin-induced vestibular hair cell damage was examined by using an in vitro LIVE/DEAD system. Results--L-NAME inhibited the production of NO, D-methionine and BDNF restricted the production of ROS and leupeptin inhibited neither NO nor ROS. All the drugs used limited the vestibular hair cell damage caused by gentamicin. The combinations L-NAME+BDNF, L-NAME+leupeptin and D-methionine+BDNF had a significantly stronger preventive effect on hair cell damage. Conclusion--It is suggested that combined treatment with a radical inhibitor and either a neurotrophin or calpain inhibitor may help to treat inner ear disorders more effectively.

• Apoptosis
• Brain-derived Neurotrophic Factor
• Free Radical
• Gentamicin
• Nitric Oxide
• Vestibular Hair Cell