title: (-)-Epigallocatechin-3-gallate protects against NO-induced ototoxicity through the regulation of caspase- 1, caspase-3, and NF-κB activation.
abstract: Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in ex vivo analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, S-nitroso-N-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome c, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague-Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity.
authors.affiliation: Department of Cosmeceutical Science, Daegu Hanny University, Kyungsan, Gyeoungbuk, Republic of Korea.
authors.forename: Su-Jin
authors.initials: SJ
authors.lastname: Kim
authors.forename: Jeong-Han
authors.initials: JH
authors.lastname: Lee
authors.forename: Beom-Su
authors.initials: BS
authors.lastname: Kim
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
authors.forename: Noh-Yil
authors.initials: NY
authors.lastname: Myung
authors.forename: Jae-Young
authors.initials: JY
authors.lastname: Um
authors.forename: Seung-Heon
authors.initials: SH
authors.lastname: Hong
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D020170:Caspase 1 / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism*; D002392:Catechin / Q000031:analogs & derivatives* / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D006198:Hair Cells, Auditory / Q000187:drug effects / Q000378:metabolism; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology* / Q000633:toxicity; D009925:Organ of Corti / Q000187:drug effects* / Q000378:metabolism*; D020011:Protective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D016328:NF-kappa B; D020011:Protective Agents; D017382:Reactive Oxygen Species; D009569:Nitric Oxide; D002392:Catechin; C045651:epigallocatechin gallate; D053148:Caspase 3; D020170:Caspase 1