Noise exposure represents the second most common cause of acquired sensorineural hearing loss and we observed that tumor necrosis factor α (TNFα) was involved in this context. The effect of Tnfα gene silencing on the expression profile related to the TNFα 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 Tnfα 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 TNFα 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 TNFα by gene silencing was useful to prevent noise-induced hearing loss.

No abstract

Bcl-2-associated X protein Bcl2 B-celllymphoma 2 BERA Brain Evoked Response Audiometry BID BH3 interacting domain death agonist BSA Bovine Serum Albumin Caspases Cysteine-dependent aspartate-specific proteases CA Califórnia Cat Catálogo cDNA DNA complementar CEUA Comissão de Ética no Uso de Animais cIAP Cellular inhibitor of apoptosis protein COBEA Colégio Brasileiro de Experimentação Animal CONCEA Conselho Nacional de Controle de Experimentação Animal Ct Cicle threshold Palavras-chave: RNA de interferência. Perda auditiva induzida por ruído. Apoptose. Fator de Necrose tumoral alfa. Audiometria de resposta evocada. Potencial evocado auditivo ABSTRACT Rodrigue JC. Effect of Tnfa gene silencing on auditory preservation in Wistar rats exposed to noise and analysis of gene expression of this metabolic pathway. [Thesis].