Inhibition of p38 mitogen-activated protein kinase ameliorates radiation-induced ototoxicity in zebrafish and cochlea-derived cell lines.
Neurotoxicology
; 40: 111-22, 2014 Jan.
Article
em En
| MEDLINE
| ID: mdl-24374476
ABSTRACT
Radiation is a widely used treatment for head and neck cancers, and one of its most severe side effects is ototoxicity. Radiation-induced ototoxicity has been demonstrated to be linked to the increased production of ROS and MAPK. We intended to investigate the effect of p38 inhibition on radiation-induced ototoxicity in cochlea-derived HEI-OC1 cells and in a zebrafish model. The otoprotective effect of p38 inhibition against radiation was tested in vitro in the organ of Corti-derived cell line, HEI-OC1, and in vivo in a zebrafish model. Radiation-induced apoptosis, mitochondrial dysfunction, and an increase of intracellular NO generation were demonstrated in HEI-OC1 cells. The p38-specific inhibitor, SB203580, ameliorated radiation-induced apoptosis and mitochondrial injury in HEI-OC1 cells. p38 inhibition reduced radiation-induced activation of JNK, p38, cytochrome c, and cleavage of caspase-3 and PARP in HEI-OC1 cells. Scanning electron micrography showed that SB203580 prevented radiation-induced destruction of kinocilium and stereocilia in zebrafish neuromasts. The results of this study suggest that p38 plays an important role in mediating radiation-induced ototoxicity and inhibition of p38 could be a plausible option for preventing radiation ototoxicity.
Palavras-chave
Apoptosis; DMEM,; DMSO,; Dulbecco's modified Eagle's medium; ERK,; FBS,; FITC,; HNSCC,; IHC,; Inner hair cell; JNK,; MAPK,; MMP,; NO,; PARP,; PBS,; PI,; ROS,; SB203580; SEM,; SNHL,; TUNEL,; c-Jun N-terminal kinase; days post-fertilization; dimethyl sulfoxide; dpf,; extracellular signal-regulated kinases; fetal bovine serum; fluorescein isothiocyanate; head and neck squamous cell carcinoma; hearing preservation; mitochondrial membrane potential; mitogen-activated protein kinase; nitric oxide; p38; p38, p38; phosphate buffered saline; poly ADP ribose polymerase; propidium iodide; radiation; reactive oxygen species; scanning electron microscopy; sensorineural hearing loss; terminal deoxynucleotidyl transferase (TdT)-mediated dUTP-biotin nick end labeling; zebrafish
Texto completo:
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Base de dados:
MEDLINE
Assunto principal:
Órgão Espiral
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Piridinas
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Lesões Experimentais por Radiação
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Proteínas Quinases p38 Ativadas por Mitógeno
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Inibidores Enzimáticos
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Imidazóis
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article