Noise-induced changes in expression levels of NADPH oxidases in the cochlea.

UNLABELLED: NADPH oxidases are enzymes that transport electrons across the plasma membrane and generate superoxide radical from molecular oxygen. The current study investigated the expression and distribution of NOX/DUOX members of the NADPH oxidase family (NOX1-5 and DUOX1-2) in the rat cochlea and their regulation in response to noise. Wistar rats (8-10 weeks) were exposed for 24 h to band noise (8-12 kHz) at moderate (100 dB) or traumatic (110 dB) sound pressure levels (SPL). Animals exposed to ambient noise (45-55 dB SPL) served as controls. Immunohistochemistry demonstrated predominant expression of all NOX/DUOX isoforms in the sensory and supporting cells of the organ of Corti, with very limited immunoexpression in the lateral wall tissues and spiral ganglion neurons. Noise exposure induced up-regulation of NOX1 and DUOX2 in the cochlea, whereas NOX3 was down-regulated. A significant reduction in the intensity of NOX3 immunolabeling was observed in the inner sulcus region of the cochlea after exposure to noise. Post-exposure inhibition of NADPH oxidases by Diphenyleneiodonium (DPI), a broadly selective NADPH oxidase inhibitor, mitigated noise-induced hearing loss.

CONCLUSION: Noise-induced up-regulation of NOX1 and DUOX2 could be linked to cochlear injury. In contrast, down-regulation of NOX3 may represent an endogenous protective mechanism to reduce oxidative stress in the noise-exposed cochlea. Inhibition of NADPH oxidases is potentially a novel pathway for therapeutic management of noise-induced hearing loss.