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
2003 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, Vol. 123, no 1, 8-13 p.Article in journal (Other (popular science, discussion, etc.)) Published
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.
Place, publisher, year, edition, pages
2003. Vol. 123, no 1, 8-13 p.
Medical and Health Sciences
IdentifiersURN: urn:nbn:se:uu:diva-73576DOI: 10.1080/0036554021000028078PubMedID: 12625566OAI: oai:DiVA.org:uu-73576DiVA: diva2:101486