New Insights on the Effect of TNF Alpha Blockade by Gene Silencing in Noise-Induced Hearing Loss

Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor alpha (TNF alpha) was involved in this context. The effect of Tnf alpha gene silencing on the expression profile related to the TNF alpha metabolic pathway in an experimental model of noise-induced hearing loss had not previously been studied. Methods: Single ears of Wistar rats were pretreated with Tnf alpha small interfering RNA (siRNA) by trans-tympanic administration 24 h before they were exposed to white noise (120 dBSPL for three hours). After 24 h of noise exposure, we analyzed the electrophysiological threshold and the amplitude of waves I, II, III, and IV in the auditory brain response click. In addition, qRT-PCR was performed to evaluate the TNF alpha metabolic pathway in the ears submitted or not to gene silencing. Results: Preservation of the electrophysiological threshold and the amplitude of waves was observed in the ears submitted to gene silencing compared to the ears not treated. Increased anti-apoptotic gene expression and decreased pro-apoptotic gene expression were found in the treated ears. Conclusion: Our results allow us to suggest that the blockade of TNF alpha by gene silencing was useful to prevent noise-induced hearing loss.