Reduction in Impulse Noise-Induced Permanent Threshold Shift with Intracochlear Application of an NADPH Oxidase Inhibitor

Abstract

Toxic levels of reactive oxygen species are key contributors to the lesion of dead outer hair cells (OHCs) seen in the cochlea after noise exposure. The current study follows previous work in which paraquat was used to demonstrate that NADPH oxidase is active in the cochlea and can contribute to cochlear reactive oxygen species formation and hair cell loss. The current study was undertaken to test whether pharmacological blockade of NADPH oxidase in the cochlea would lead to reduced noise-induced hearing loss and OHC death. A total of 18 chinchillas (36 ears) were assessed in the study. AEBSF (4-[2-aminoethyl]benzenesulfonyl fluoride), an inhibitor of NADPH oxidase activation, was dissolved in distilled water and delivered into the cochlea via diffusion across the round window membrane. The contralateral ears received distilled water as a vehicle control. Following treatment, chinchillas were exposed to one of two noises: a 4 kHz octave band noise at 106 dB SPL for 6 hr or an impulse noise that consisted of 75 pairs of 155 dB pSPL impulses. Pre- and post-noise exposure, thresholds of the auditory brainstem response at 2-8 kHz were measured. Postmortem OHC counts were conducted at the conclusion of the study. Two- and three-factor ANOVAs were used for statistical analysis of the OHC losses and ABR threshold shifts induced by the noise exposures. Permanent threshold shift from the impulse noise was reduced in the ears treated with the NADPH oxidase inhibitor, but no differences were found in the groups exposed to the continuous noise. OHC losses were not statistically different between the treated and untreated ears for either noise exposure. The results suggest that NADPH oxidase-mediated superoxide has a role in cochlear damage from impulse noise, and pharmacologic inhibition of NADPH oxidase can reduce cochlear susceptibility to noise damage. The lack of protection from the longer-duration continuous noise can be attributed to a number of possibilities related to dose level and delivery schedule.