A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma. - Inserm - Institut national de la santé et de la recherche médicale Accéder directement au contenu
Article Dans Une Revue Neuropharmacology Année : 2007

A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma.

Résumé

Free radical and calcium buffering mechanisms are implicated in cochlear cell damage that has been induced by sound trauma. Thus in this study we evaluated the therapeutic effect of a novel dual inhibitor of calpains and of lipid peroxidation (BN 82270) on the permanent hearing and hair cell loss induced by sound trauma. Perfusion of BN 82270 into the scala tympani of the guinea pig cochlea prevented the formation of calpain-cleaved fodrin, translocation of cytochrome c, DNA fragmentation and hair cell degeneration caused by sound trauma. This was confirmed by functional tests in vivo, showing a clear dose-dependent reduction of permanent hearing loss (ED(50)=4.07muM) with almost complete protection at 100muM. Furthermore, BN82270 still remained effective even when applied onto the round window membrane after sound trauma had occurred, within a therapeutic window of 24h. This indicates that BN 82270 may be of potential therapeutic value in treating the cochlea after sound trauma.
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Dates et versions

inserm-00145385 , version 1 (11-05-2007)

Identifiants

Citer

Jing Wang, Bernadette Pignol, Pierre-Etienne Chabrier, Takaomi Saido, Ruth Lloyd, et al.. A novel dual inhibitor of calpains and lipid peroxidation (BN82270) rescues the cochlea from sound trauma.. Neuropharmacology, 2007, 52 (6), pp.1426-37. ⟨10.1016/j.neuropharm.2007.02.007⟩. ⟨inserm-00145385⟩
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