Noise-Induced Hearing Loss: Overview and Future Prospects for Research on Oxidative Stress

Abstract

Noise-induced hearing loss (NIHL) is a common type of sensorineural hearing loss caused by exposure to high-intensity noise that leads to irreversible cochlear damage. Despite extensive research on cochlear pathophysiology, the precise mechanisms remain unclear, and no established treatment exists. This is due to the challenges in imaging and the inability to perform biopsies in human patients. Consequently, animal models, particularly mice, have been widely used to study NIHL. Clinically, NIHL presents as either a temporary threshold shift, in which hearing recovers, or a permanent threshold shift, which results in an irreversible loss. Histopathological studies have identified the key features of NIHL, including outer hair cell loss, auditory nerve degeneration, and synaptic impairment. Recent findings suggest that oxidative stress and inflammation are major contributors to NIHL, highlighting the potential for therapeutic interventions, such as antioxidants and anti-inflammatory agents. Given the increasing prevalence of NIHL owing to occupational noise exposure and personal audio device use, addressing this issue is a pressing public health challenge. This review summarizes the clinical features, underlying mechanisms, and emerging treatment strategies for NIHL while identifying current knowledge gaps and future research directions.

Keywords: acoustic trauma; antioxidant; reactive oxygen species (ROS).

Figure 1

Histological differences between temporary threshold shift (TTS) and permanent threshold shift (PTS). In TTS, the hair cells remain intact; however, ribbon synapses are damaged and become detached. Additionally, supporting cells undergo buckling, causing some outer hair cells to become detached from the tectorial membrane. When noise exposure is more intense or repeated, hair cells’ and supporting cells’ death and the auditory nerve’s degeneration can produce an irreversible condition, leading to PTS.

Figure 2

Molecular mechanisms of noise-induced hearing loss and potential therapeutic targets. The pathogenesis of noise-induced hearing loss (NIHL) involves multiple mechanisms, including oxidative stress, inflammatory responses, and ischemia-induced hair cell death, as well as calcium stress and glutamatergic excitotoxicity, which contribute to synaptic damage. Several pharmacological agents have been proposed as potential therapeutic candidates for NIHL, including mito-TEMPO (MT), a mitochondria-targeted superoxide dismutase (SOD) mimetic that mitigates oxidative stress; 6-fluoro-9-methyl-pyridoindole (AC102), which has demonstrated neuroprotective effects; and calpain inhibitor MDL-28170, which suppresses calpain-mediated apoptosis and preserves cochlear integrity. In the figure, arrows indicate interactions between components. Activation arrows (→) represent stimulatory effects, while inhibitory arrows (⊣) represent suppressive effects.