The primary site of lesion induced by noise exposure is the hair cells in the organ of Corti and the primary neural degeneration occurs in synaptic terminals of cochlear nerve fibers and spiral ganglion cells. The cellular basis of
noise-induced hearing loss is oxidative stress, which refers to a severe disruption in the balance between the production of
free radicals and
antioxidant defense system in the cochlea by excessive production of
free radicals induced by noise exposure. Oxidative stress has been identified by a variety of
biomarkers to label
free radical activity which include four-hydroxy-2-nonenal,
nitrotyrosine, and
malondialdehyde, and
inducible nitric oxide synthase,
cytochrome-C, and cascade-3, 8, 9. Furthermore, oxidative stress is contributing to the necrotic and apoptotic cell deaths in the cochlea. To counteract the known mechanisms of pathogenesis and oxidative stress induced by noise exposure, a variety of
antioxidant drugs including
oxygen-based
antioxidants such as N-acetyl-L-cystein and
acetyl-L-carnitine and nitrone-based
antioxidants such as
phenyl-N-tert-butylnitrone (PBN),
disufenton sodium, 4-hydroxy PBN, and 2, 4-disulfonyl PBN have been used in our laboratory. These
antioxidant drugs were effective in preventing or treating
noise-induced hearing loss. In combination with other
antioxidants,
antioxidant drugs showed a strong synergistic effect. Furthermore, successful use of
antioxidant drugs depends on the optimal timing of treatment and the
duration of treatment, which are highly related to the time window of
free radical formation induced by noise exposure.