The Mitigation of Noise-Induced Hearing Loss with Adenosine Amine Congener

Abstract

Noise-induced hearing loss occurs due to exposure to intense sounds. There is a ‘window of opportunity’ after noise exposure in which interventions could potentially contain the extent of permanent hearing loss that develops. One such potential therapy is the use of the drug adenosine amine congener (ADAC), which has been shown to be an effective “rescue agent” following traumatic noise exposure. The aim of this study was to further establish the potential of ADAC as a treatment for noise-induced hearing loss. Varying doses of ADAC (25-300 μg/kg) were systemically administered (i.p.) to rats after exposure to traumatic noise (8-16 kHz, 110 dB, 2 hours). Treatments were administered daily for five consecutive days, beginning six hours after the cessation of noise exposure. Hearing sensitivity was assessed with auditory brainstem response thresholds (at 4-28 kHz), which were measured before, and 12 days after noise exposure. All the doses tested in the present study were effective in mitigating noise-induced hearing loss, with 100 and 200 μg/kg ADAC treatment being the most effective, providing 19 dB and 17 dB protection (averaged across the measured frequencies), respectively. Administration of the two highest doses of ADAC, 200 and 300 μg/kg, was accompanied by behavioural changes and reductions in body temperature. However, this was minimal (<1oC) and did not induce any obvious signs of distress, with rats gaining similar body weight throughout the experimental procedure in all the groups. Qualitative analysis of hair cell loss demonstrated that the amount of hair cell loss was relatively consistent with the amount of threshold shift, with ADAC-treated cochleae showing greater preservation of hair cells. Despite limiting noise-induced hearing loss and improving the survival of sensory hair cells, reductions in ABR wave I amplitudes were observed in all the ADAC-treated groups, suggesting that ADAC and has limited effect on spiral ganglion neuron survival. Future pre-clinical research is needed to further establish ADAC as a treatment for NIHL, including determining the most effective method of administering ADAC, potential side effects and clarifying the effects of ADAC on the survival of spiral ganglion neurons.