title: The beneficial effect of Hangesha-shin-to (TJ-014) in gentamicin-induced hair cell loss in the rat cochlea.
abstract: OBJECTIVE
  Ototoxic damage caused by aminoglycosides (AG) leads to the loss of cochlear hair cells (HCs). In mammals, mature cochlear HCs are unable to regenerate, and their loss results in permanent hearing deficits. Our objective was to protect the inner ear from damage after an AG challenge. The generation of reactive oxygen species (ROS), one of the earliest events in the process of AG ototoxicity, is considered to play a key role in the initiation of HC death. We examined whether Hangesha-shin-to (TJ-014), a traditional Japanese Kampo medicine considered to be a potent antioxidant, protects HCs from gentamicin (GM)-induced damage.
  
  
  METHODS
  Organ of Corti explants removed from postnatal day 3-5 rats were maintained in tissue culture and exposed to 50μM GM for up to 48h. The effects of TJ-014 on GM-induced ototoxicity were assessed by HC counts and immunohistochemistry against cleaved caspase-3, 8-hydroxy-2'-deoxyguanosine (8-OHdG), and a probe reacting to mitochondrial function changes.
  
  
  RESULTS
  TJ-014 treatments significantly reduced GM-induced HC loss and immunoreactivities for cleaved caspase-3 and 8-OHdG; these effects were correlated with increasing TJ-014 concentrations. Moreover, TJ-014 protected the mitochondrial membrane potential from GM ototoxicity.
  
  
  CONCLUSIONS
  These findings indicate the potential of TJ-014 to prevent GM-induced cochlear damage involving ROS.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Katsuki
authors.initials: K
authors.lastname: Niwa
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan; Division of Otolaryngology, New Tokyo Hospital, 1271 Wanagaya, Matsudo, Japan. Electronic address: t-matsunobu@shin-tokyohospital.or.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Matsunobu
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Takaomi
authors.initials: T
authors.lastname: Kurioka
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kamide
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Tamura
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Shin
authors.initials: S
authors.lastname: Tadokoro
authors.affiliation: Department of Anesthesiology, National Defense Medical College, 3-2 Namiki, Tokorozawa, Japan.
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Satoh
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, National Defense Medical College, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Shiotani
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D000818:Animals; D000900:Anti-Bacterial Agents / Q000633:toxicity*; D053148:Caspase 3 / Q000187:drug effects / Q000378:metabolism; D002452:Cell Count; D003051:Cochlea / Q000187:drug effects / Q000378:metabolism; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000378:metabolism; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005839:Gentamicins / Q000633:toxicity*; D006198:Hair Cells, Auditory / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D007150:Immunohistochemistry; D008928:Mitochondria / Q000187:drug effects; D009925:Organ of Corti / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000900:Anti-Bacterial Agents; D004365:Drugs, Chinese Herbal; D005839:Gentamicins; C088236:hange-shashinto; D000080242:8-Hydroxy-2'-Deoxyguanosine; C505410:Casp3 protein, rat; D053148:Caspase 3; D003849:Deoxyguanosine
keywords: Cochlea; Gentamicin; Hair cell; Hangesha-shin-to; TJ-014