Quinolylnitrone 23 Protects from Auditory Cell Oxidative Injury and Noise-Induced Hearing Loss

Oxidative stress is a key pathogenic mechanism in noise-induced hearing loss, occurring when the production of free radicals in the cochlea overwhelms its antioxidant defenses. Thus, antioxidant molecules, including <i>N</i>-acetyl-l-cysteine, acetyl-L-carnitine, resveratrol, HPN-07, and 4-OHPBN nitrones, have been explored as otoprotective agents with limited success. A novel quinolylnitrone derivative QN23 has been shown to suppress oxidative stress in ischemic stroke. In this study, we show that QN23 was not ototoxic and protected from oxidative stress both <i>in vitro</i> in the cochlear HEI-OC1 cell line and <i>in vivo</i> in mice. QN23 increased HEI-OC1 cell survival after H₂O₂-induced oxidative stress, showing better effectiveness than <i>N</i>-acetyl-l-cysteine. Systemic administration of QN23 in mice was well-tolerated, and significantly reduced acute auditory threshold shifts 1 day postnoise exposure. The protective effects of QN23 were dose- and time-dependent, with optimal results observed when administered twice daily for 3 days, starting 1 h prior to noise exposure. This protection was associated with the duration of the treatment. QN23 normalized the expression of cochlear genes associated with oxidative stress and inflammation, such as <i>Nrf2</i>, <i>Hmox1</i>, <i>Nqo1</i>, <i>Nlrp3</i>, <i>Tnfa</i>, <i>Il1b</i>, <i>Dusp1</i>, and <i>Kim1</i>, among others, counteracting immediate noise-induced molecular alterations. These results suggest that QN23 effectively mitigates cochlear oxidative damage and that early intervention can block critical molecular changes induced by noise, thereby preserving hearing.