Expression and Roles of Free Radicals and Reactive Oxygen Species in Hearing Loss.

OBJECTIVE: Although the etiologies and pathogenesis of common hearing disorders-noise-induced hearing loss (NIHL), age-related hearing loss (ARHL), and idiopathic sudden sensorineural hearing loss (ISSNHL)-are diverse, accumulating evidence indicates that reactive oxygen species (ROS) contribute to hearing loss and that antioxidants may help prevent or treat it. We conducted a literature review to examine the relationship between hearing loss and ROS/free radicals in both humans and animal models. METHODS: We performed a comprehensive literature search of PubMed/MEDLINE, Embase, the Cochrane Library, Scopus, and Google Scholar to evaluate the induction and role of ROS in the development and treatment of hearing loss. RESULTS: We synthesized evidence across NIHL, ARHL, and ISSNHL. Factors and reactive species implicated in hearing loss included cytomegalovirus infection, genetic polymorphisms, NADPH oxidase 4 (NOX4), NOX transgenic models (NOX-Tg), lipid hydroperoxides (LOOH), and malondialdehyde (MDA). Antioxidant strategies examined for prevention or treatment included vitamins A, C, and E with magnesium; rebamipide; α-lipoic acid; LLY-283; edaravone; melatonin; glutathione peroxidase; superoxide dismutase; glucose; hydrogen-saturated saline; activation of nuclear factor erythroid 2-related factor 2 (Nrf2); inhaled hydrogen gas; and caffeic acid. CONCLUSIONS: Elevated ROS and free radicals appear to contribute to the pathogenesis of hearing loss. Although definitive conclusions cannot yet be drawn, current evidence suggests that antioxidant approaches may aid in prevention and treatment. Further studies are needed to elucidate underlying mechanisms, refine therapeutic targets and dosing, and validate efficacy in rigorously designed clinical trials.