EPICATECHIN INHIBITS RADIATION-INDUCED AUDITORY CELL DEATH BY SUPPRESSION OF REACTIVE OXYGEN SPECIES GENERATION

Radiation-induced toxicity limits the delivery of high-dose radiation to head and neck lesions. The aim of this study was to investigate the effectiveness of epicatechin (EC), a minor component of green tea extract, on radiation-induced ototoxicity in vitro and in vivo. The effect of EC on radiation-induced cytotoxicity was analyzed in the organ of Corti-derived cell lines, HEI-OC1 and UB-OC1. The cell viability, apoptosis, reactive oxygen species generation, and mitochondrial membrane potential as well as changes in the signal pathway related to apoptosis were investigated. Then, the therapeutic effects of hearing protection and drug toxicity of EC were explored in a zebrafish and rat model. Radiation-induced apoptosis and altered mitochondrial membrane potential in HEI-OC1 and UB-OC1 were observed. EC inhibited radiation-induced apoptosis and intracellular reactive oxygen species generation. EC markedly attenuated the radiation-induced embryotoxicity and protected against radiation-induced loss and changes of auditory neuromast in the zebrafish. In addition, intratympanic administration of EC was protective against radiation-induced hearing loss in the rat model, as determined by click-evoked auditory brainstem (P<0.01). EC significantly reduced the expression of p-JNK, p-ERK cleaved caspase-3, and cleaved PARP compared to their significant increase after radiation treatment. The results of this study suggest that EC significantly inhibited radiation-induced apoptosis in auditory hair cells and may be a safe and effective candidate treatment for the prevention of radiation-induced ototoxicity. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.