XKR8 Deletion Protects Against Noise-Induced Hearing Loss by Attenuating Apoptosis and Preserving Mitochondrial Bioenergetics in the Cochlea.

This study elucidated the role of the XKR8 gene in noise-induced hearing loss (NIHL) through animal experiments, PCR experiments, inner ear morphological experiments, ATP and mitochondrial complex I and II assays, and Western blotting experiments. The results showed that pre-exposure ABR showed no significant difference in baseline hearing thresholds between XKR8-/-and WT mice (P > 0.05). On day 1 post-exposure, ABR results indicated hearing thresholds around 85 dB in both groups. On days 3, 7, and 14, XKR8-110 dB mice had lower hearing thresholds than WT-110 dB mice (P < 0.05). Immunofluorescence showed less OHC loss in the Middle posterior and Base regions and more IHC synapses in XKR8-110 dB mice than WT-110 dB mice (P < 0.05). ATP content and activities of mitochondrial complexes I and II were significantly reduced in both noise-exposed groups compared to unexposed groups (P < 0.05), but XKR8-110 dB mice had higher levels (P < 0.05). Western blot showed higher BAX, caspase-3, and caspase-8 expression and lower BCL-2 expression in noise-exposed groups (P < 0.05). XKR8-110 dB mice had lower expression of these proteins and higher BCL-2 expression than WT-110 dB mice (P < 0.05). TNF-α expression was lower in XKR8-110 dB mice than in WT-110 dB mice (P < 0.05), while IL-6 expression showed no significant difference (P > 0.05). These findings demonstrate that the XKR8 gene mitigates noise-induced hearing damage by reducing hair cell apoptosis and energy depletion, highlighting the significant role of the XKR8 gene in NIHL. XKR8 deletion can mitigate noise-induced hearing damage by reducing hair cell apoptosis and energy depletion, highlighting the significant role of the XKR8 gene in NIHL.