CD38 coordinates with NF-κB to promote cochlear inflammation in noise-induced hearing loss：the protective effect of Apigenin

Abstract

Abstract Noise exposure is one of the most common scause of sensorineural hearing loss. Although a large number of studies considered inflammation as a major contributor to noise-induced hearing loss, the process of cochlear inflammation is still unclear. Studies have found that activation of the NF-κB signal caused the accumulation of macrophages in the inner ear plays an important role in hair cell damage. In this study, Tandem Mass Tag (TMT) technique was used to analyze the changes of basilar membrane proteome expression before and after acoustic injury. After noise exposure, Nicotinamide Adenine Dinucleotide (NAD) metabolism level was down-regulated and NF-κB signal pathway was activated. It seemed that the expression of CD38, the main NAD hydrolase in mammals, could straightly lead to the inflammation onset. Then Anakinra, an IL-1 receptor blocker, and Apigenin, a CD38 inhibitor, were given to animals to protect noise induced hearing loss. Our results showed that Anakinra had a littlt influence on the hearing threshold shift, while Apigenin could significantly reduce the threshold shift of hearing by inhibiting the activation of NF-κB and CD38. These results suggest that inhibition of the expression of NF-κB and CD38 can be a promising target for protecting noise-induced hearing loss.