Therapeutic Function of Liraglutide for Mitigation of Blast-Induced Hearing Damage: An Initial Investigation in Animal Model of Chinchilla.

Abstract

Auditory injuries induced by repeated exposures to blasts reduce the operational performance capability and the life quality of military personnel. The treatment for blast-induced progressive hearing damage is lacking. We have recently investigated the therapeutic function of liraglutide, a glucagon-like peptide-1 receptor agonist, to mitigate blast-induced hearing damage in the animal model of chinchilla, under different blast intensities, wearing earplugs (EPs) or not during blasts, and drug-treatment plan. The goal of this study was to investigate the therapeutical function of liraglutide by comparing the results obtained under different conditions. Previous studies on chinchillas from two under-blast ear conditions (EP/open), two blast plans (G1: 6 blasts at 3-5 psi or G2:3 blasts at 15-25 psi), and three treatment plans (blast control, pre-blast drug treatment, and post-blast drug treatment) were summarized. The auditory brainstem response (ABR), distortion product otoacoustic emission (DPOAE), and middle latency response (MLR) recorded within 14 days after the blasts were used. Statistical analysis was performed to evaluate the effect of liraglutide under different conditions. ABR threshold shifts indicated that the conditions of the EP and open ears were substantially different. Results from EP chinchillas indicated that the pre-blast treatment reduced the acute ABR threshold elevation on the day of blasts, and the significance of such an effect increased with the blast level. Liraglutide-treated open chinchillas showed lower ABR threshold shifts at the later stage of the experiment regardless of the blast levels. The DPOAE was less damaged after G2 blasts compared to G1 when pre-blast liraglutide was administrated. Lower post-blast MLR amplitudes were observed in the pre-blast treatment groups. This study indicated that the liraglutide mitigated the blast-induced auditory injuries. In EP ears, the pre-blast administration of liraglutide reduced the severity of blast-induced acute damage in ears with EP protection, especially under G2. In animals with open ears, the effect of liraglutide on the restoration of hearing increased with time. The liraglutide potentially benefits post-blast hearing through multiple approaches with different mechanics.