N-Acetylcysteine and N-Nitroarginine Methyl Ester Attenuate Carboplatin-Induced Ototoxicity in Dissociated Spiral Ganglion Neuron Cultures
Clinical and Experimental Otorhinolaryngology
;
: 11-17, 2011.
Article
in English
| WPRIM
| ID: wpr-133462
ABSTRACT
OBJECTIVES:
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.CONCLUSION:
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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Acetylcysteine
/
Spiral Ganglion
/
Carboplatin
/
Neurites
/
Reactive Oxygen Species
/
NG-Nitroarginine Methyl Ester
/
Hair
/
Ligases
/
Lysine
/
Neurons
Limits:
Animals
Language:
English
Journal:
Clinical and Experimental Otorhinolaryngology
Year:
2011
Type:
Article
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