Objective: The pathophysiology of noise-induced hearing loss (NIHL) encompasses excessive inflammation, tissue damage, production of reactive oxygen species, and apoptotic processes, culminating in irreversible damage to hair cells. Currently, no clinical interventions are available to mitigate this condition. Alpha1-antitrypsin (AAT) is a circulating molecule with tissue-protective properties that increases during inflammatory states and facilitates the resolution of inflammation. Transgenic mice expressing elevated levels of human AAT have demonstrated enhanced tissue repair in various in vivo models, including restoration of vestibular function following inner ear trauma. We hypothesized that the transgenic overexpression of human AAT would offer protection against permanent threshold shifts following noise exposure in mice, as compared to wild-type controls. Study Design: A murine model of NIHL. Setting: Laboratory study. Methods: Wild-type C57BL/6 and transgenic mice expressing human AAT (n = 5 per group) were exposed to broadband noise at a sound pressure level of 100 dB SPL for 2 hours. Auditory brainstem responses were measured. Results: hAAT mice showed a greater threshold shift at 24 hours but near-complete recovery by Day 7, unlike WT mice that developed a permanent threshold shift. Conclusions: hAAT promotes recovery after acoustic trauma, suggesting a potential therapeutic role in NIHL. WT and hAAT groups had similar baseline thresholds. At 24 hours postnoise exposure, hAAT mice exhibited a greater threshold shift than WT mice. By Day 7, hAAT thresholds had nearly recovered to baseline, whereas WT thresholds remained elevated, consistent with permanent hearing loss. Further research is required to elucidate the protective effects of AAT on the inner ear.
Kaminer et al. (Wed,) studied this question.