Objective:Molecular hydrogen (H2) has shown therapeutic potential in several oxidative stress-related conditions in humans, is well-tolerated, and is easily administered via inhalation.The aim of this preclinical in vivo study was to investigate whether impulse noise trauma can be prevented by H2when inhaled immediately after impulse noise exposure.Methods:Guinea pigs (n = 26) were subjected to impulse noise (n = 400; 156 dB SPL; 0.33/s; n = 11; the Noise group), to impulse noise immediately followed by H2inhalation (2 mol%; 500 ml/min; 1 hour; n = 10; the Noise + H2group), or to H2inhalation (n = 5; the H2group). The acoustically evoked ABR threshold at 3.15, 6.30, 12.5, 20.0, and 30.0 kHz was assessed before and 4 days after impulse noise and/or H2exposure. The cochleae were harvested after the final ABR assessment for quantification of hair cells.Results:Noise exposure caused ABR threshold elevations at all frequencies (median 35, 35, 30, 35, and 35 dB SPL, the Noise group; 20, 25, 10, 13, and 20 dB SPL, the Noise + H2group;P< .05) but significantly less so in the Noise + H2group (P< .05). Outer hair cell (OHC) loss was in the apical, mid, and basal regions 8.8%, 53%, and 14% in the Noise group and 3.5%, 22%, and 1.2% in the Noise + H2group. The corresponding inner hair cell (IHC) loss was 0.1%, 14%, and 3.5% in the Noise group and 0%, 2.8%, and 0% in the Noise + H2group. The difference between the groups was significant in the basal region for OHCs (P= .003) and apical (P= .033) and basal (P= .048) regions for IHCs.Conclusions:Acute acoustic trauma can be reduced by H2when inhaled immediately after impulse noise exposure.