title: N-acetylcysteine and N-nitroarginine methyl ester attenuate Carboplatin-induced ototoxicity in dissociated spiral ganglion neuron cultures.
abstract: OBJECTIVE
  Carboplatin, a platinum-containing anti-cancer drug used to treat a variety of cancers, induces ototoxicity. Since, reactive oxygen species (ROS) and nitric oxide (NO) seem to be responsible for this toxicity, the antioxidant, N-acetyl-L-cysteine (L-NAC), and NO synthetase inhibitor, N-nitro-L-arginine methyl ester (L-NAME) were predicted to have protective effects against carboplatin ototoxicity. The aim of this study was to test for the protective effects of L-NAC and L-NAME on cochlear hair cells and spiral ganglion neurons (SGNs).
  
  
  METHODS
  Cochlear organotypic cultures and dissociated spiral ganglion neuron cultures, from mice postnatal day 5 cultures were used in this study. The cultures were treated with carboplatin alone or in combination with L-NAC or L-NAME, and carboplatin-induced damage was monitored.
  
  
  RESULTS
  Treatment with carboplatin induced a significant loss of outer hair cells, while inner hair cells were preserved in the cochlear organotypic cultures. Addition of L-NAC or L-NAME reduced the amount of carboplatin-induced hair cell damage; the differences did not reach statistical significance. However, carboplatin significantly decreased the number of surviving SGNs in dissociated cultures. The toxic effects were significantly reduced by addition of L-NAC or L-NAME. In addition, carboplatin induced the loss of neurites from the SGN somata, and this was not blocked with L-NAC or L-NAME.
  
  
  CONCLUSIONS
  The results of this study suggest that ROS and NO are involved in carboplatin-induced damage to hair cells and SGNs, and administration of L-NAC/L-NAME can be used to attenuate the toxicity.
authors: Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors: Il Joon
authors: IJ
authors: Moon
authors: Ki Ryung
authors: KR
authors: Kim
authors: Ho-Suk
authors: HS
authors: Chu
authors: Se Hyung
authors: SH
authors: Kim
authors: Won-Ho
authors: WH
authors: Chung
authors: Yang-Sun
authors: YS
authors: Cho
authors: Sung Hwa
authors: SH
authors: Hong