N-Acetylcysteine and N-Nitroarginine Methyl Ester Attenuate Carboplatin-Induced Ototoxicity in Dissociated Spiral Ganglion Neuron Cultures
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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 LNAC 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 LNAME. In addition, carboplatin induced the loss of neurites from the SGN somata, and this was not blocked with LNAC 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.
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 LNAC 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 LNAME. In addition, carboplatin induced the loss of neurites from the SGN somata, and this was not blocked with LNAC 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.
참고문헌 (31)
- Ahmed SM, "Treatment of squamous cell carcinoma of the head and neck in the metastatic and refractory settings: advances in chemotherapy and the emergence of small molecule epidermal growth factor receptor kinase inhibitors", Curr Cancer Drug Targets, 7(7), pp.666~673 (2007)
- Goffin J, "Lung Cancer Disease Site Group of Cancer Care Ontario’s Program in Evidence-Based Care. First-line systemic chemotherapy in the treatment of advanced non-small cell lung cancer: a systematic review", J Thorac Oncol, 5(2), pp.260~274 (2010)
- Marchetti C, "First-line treatment of advanced ovarian cancer: current research and perspectives", Expert Rev Anticancer Ther, 10(1), pp.47~60 (2010)
- Esteban-Fernandez D, "Accumulation, fractionation, and analysis of platinum in toxicologically affected tissues after cisplatin, oxaliplatin, and carboplatin administration", J Anal Toxicol, 32(2), pp.140~146 (2008)
- Crepaldi de Almeida EO, "High frequency audiometric study in cancer-cured patients treated with cisplatin", Braz J Otorhinolaryngol, 74(3), pp.382~390 (2008)
- Dean JB, "Hearing loss in pediatric oncology patients receiving carboplatin-containing regimens", J Pediatr Hematol Oncol, 30(2), pp.130~134 (2008)
- Husain K, "Carboplatin-induced oxidative stress in rat cochlea", Hear Res, 159(1), pp.14~22 (2001)
- Kelly TC, "Aminoguanidine reduces cisplatin ototoxicity", Hear Res, 186(1), pp.10~16 (2003)
- Okur E, "Effect of N-acetylcysteine on carboplatin-induced ototoxicity and nitric oxide levels in a rat model", Laryngoscope, 117(12), pp.2183~2186 (2007)
- Rahman Q, "Glutathione redox system in oxidative lung injury", Crit Rev Toxicol, 29(6), pp.543~568 (1999)
- Coleman JK, "Pharmacological rescue of noise induced hearing loss using N-acetylcysteine and acetyl-L-carnitine", Hear Res, 226(1), pp.104~113 (2007)
- Shi X, "The electrochemical and fluorescence detection of nitric oxide in the cochlea and its increase following loud sound", Hear Res, 164(1), pp.49~58 (2002)
- Diao M, "Nitric oxide synthase inhibitor reduces noiseinduced cochlear damage in guinea pigs", Acta Otolaryngol, 127(11), pp.1162~1167 (2007)
- i within a set range, "J Neurosci", 1997, 1959~1970
- Kushner BH, "Ototoxicity from high-dose use of platinum compounds in patients with neuroblastoma", Cancer, 107(2), pp.417~422 (2006)
- Kim HJ, "Roles of NADPH oxidases in cisplatin-induced reactive oxygen species generation and ototoxicity", J Neurosci, 30(11), pp.3933~3946 (2010)
- Lee JE, "Role of reactive radicals in degeneration of the auditory system of mice following cisplatin treatment", Acta Otolaryngol, 124(10), pp.1131~1135 (2004)
- Li G, "Cisplatin ototoxicity to the rat inner ear: a role for HMG1 and iNOS", Neurotoxicology, 27(1), pp.22~30 (2006)
- Yamane H, "Nitric oxide induces apoptosis of the hair cells of cochlea", Acta Otolaryngol Suppl, (554), pp.6~11 (2004)
- Watanabe K, "Nuclear-factor kappa B (NF-kappa B)-inducible nitric oxide synthase (iNOS", NOS II) pathway damages the stria vascularis in cisplatin-treated mice, 2002, pp.22(6C), 4081~4085
- Takeno S, "Degeneration of spiral ganglion cells in the chinchilla after inner hair cell loss induced by carboplatin", Audiol Neurootol, 3(5), pp.281~290 (1998)
- Jirsova K, "Differences in the inhibition of neuritic outgrowth in organotypic cultures of rat foetal dorsal root ganglia treated with cisplatin and carboplatin: a comparative study", Folia Histochem Cytobiol, 35(4), pp.215~219 (1997)
- Munnamalai V, "Reactive oxygen species regulate F-actin dynamics in neuronal growth cones and neurite outgrowth", J Neurochem, 108(3), pp.644~661 (2009)
- Evangelopoulos ME, "A role of nitric oxide in neurite outgrowth of neuroblastoma cells triggered by mevastatin or serum reduction", Neurosci Lett, 468(1), pp.28~33 (2010)
- Ohinata Y, "Protection from noise-induced lipid peroxidation and hair cell loss in the cochlea", Brain Res, 966(2), pp.265~273 (2003)
- Ding DL, "Selective loss of inner hair cells and type-I ganglion neurons in carboplatin-treated chinchillas. Mechanisms of damage and protection", Ann N Y Acad Sci, 884, pp.152~170 (1999)
- Taudy M, "Carboplatin and cisplatin ototoxicity in guinea pigs", Audiology, 31(5), pp.293~299 (1992)
- Wake M, "Carboplatin ototoxicity: an animal model", J Laryngol Otol, 107(7), pp.585~589 (1993)
- Watanabe KC, "Carboplatin induces less apoptosis in the cochlea of guinea pigs than cisplatin", Chemotherapy, 48(2), pp.82~87 (2002)
- Saito T, "Ototoxicity of carboplatin in guinea pigs", Auris Nasus Larynx, 16(1), pp.13~21 (1989)
- Kintzel PE, "Anticancer drug-induced kidney disorders", Drug Saf, 24(1), pp.19~38 (2001)