N-Acetylcysteine and N-Nitroarginine Methyl Ester Attenuate Carboplatin-Induced Ototoxicity in Dissociated Spiral Ganglion Neuron Cultures.
- Author:
Il Joon MOON
1
;
Ki Ryung KIM
;
Ho Suk CHU
;
Se Hyung KIM
;
Won Ho CHUNG
;
Yang Sun CHO
;
Sung Hwa HONG
Author Information
1. Department of Otorhinolaryngology-Head and Neck Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea. hongsh@skku.edu
- Publication Type:Original Article
- Keywords:
Ototoxicity;
Carboplatin;
Nitric oxide;
Spiral ganglion neuron;
Inner hair cell;
Outer hair cell;
Mouse
- MeSH:
Acetylcysteine;
Animals;
Carboplatin;
Hair;
Ligases;
Lysine;
Mice;
Neurites;
Neurons;
NG-Nitroarginine Methyl Ester;
Nitric Oxide;
Reactive Oxygen Species;
Spiral Ganglion
- From:Clinical and Experimental Otorhinolaryngology
2011;4(1):11-17
- CountryRepublic of Korea
- Language:English
-
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.
