Noise-induced hearing loss (NIHL) is primarily driven by inflammatory processes within the cochlea, where noise exposure triggers the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome, leading to an inflammatory cascade. The interaction between increased NLRP3 expression and NF-κB activity can further amplify cochlear inflammation. Our findings reveal that (R)-PFI-2 hydrochloride, a selective inhibitor of the SETD7 enzyme, effectively inhibits the activation of the cochlear NF-κB pathway, suppresses the release of pro-inflammatory factors, and prevents inflammasome assembly. This intervention disrupts the perpetuating cycle of inflammation, thereby alleviating damage to cochlear hair cells attributed to acoustic trauma. Consequently, (R)-PFI-2 hydrochloride emerges as a promising pharmacological candidate for NIHL, targeting and moderating the excessive immune and inflammatory responses implicated in the pathology of hearing loss.
Keywords: (R)-PFI-2 hydrochloride; NF-κB; NIHL; NLRP3; SETD7.
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