Abstract
Excessive nitric oxide (NO) production is toxic to the cochlea and induces hearing loss. However, the mechanism through which NO induces ototoxicity has not been completely understood. The aim of this study was to gain further insight into the mechanism mediating NO-induced toxicity in auditory HEI-OC1 cells and in ex vivo analysis. We also elucidated whether and how epigallocatechin-3-gallate (EGCG), the main component of green tea polyphenols, regulates NO-induced auditory cell damage. To investigate NO-mediated ototoxicity, S-nitroso-N-acetylpenicillamine (SNAP) was used as an NO donor. SNAP was cytotoxic, generating reactive oxygen species, releasing cytochrome c, and activating caspase-3 in auditory cells. NO-induced ototoxicity also mediated the nuclear factor (NF)-κB/caspase-1 pathway. Furthermore, SNAP destroyed the orderly arrangement of the 3 outer rows of hair cells in the basal, middle, and apical turns of the organ of Corti from the cochlea of Sprague–Dawley rats at postnatal day 2. However, EGCG counteracted this ototoxicity by suppressing the activation of caspase-3/NF-κB and preventing the destruction of hair cell arrays in the organ of Corti. These findings may lead to the development of a model for pharmacological mechanism of EGCG and potential therapies against ototoxicity.
Highlights
Nitric oxide (NO) plays essential roles in the physiological functions of the inner ear, including regulation of neurotransmission and blood flow [1]
To investigate the effect of NO on the arrangement of hair cells, organs of Corti isolated from rat cochlea at postnatal day 2 were treated with an NO donor (SNAP)
For the first time, that EGCG is effective in preventing the destruction of hair cell arrays and apoptosis both in vitro and ex vivo
Summary
Nitric oxide (NO) plays essential roles in the physiological functions of the inner ear, including regulation of neurotransmission and blood flow [1]. Accumulating evidence has suggested that excessive NO production may cause hearing impairment [2,3]. Noise-induced hearing loss can be caused by increased NO production in the inner ear, leading to auditory cell destruction [4,5,6]. Previous studies have suggested that treating animals with ascorbic acid, an agent that attenuates noise-induced hearing loss, reduces the concentration of NO [7]. These results indicate that excessive NO production may play an important role in pathological damage to the cochlea and elevated hearing thresholds. The correlation between hearing loss and NO production has been described in vitro and in vivo, the mechanism through which NO mediates ototoxicity has not been completely understood
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