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

Int J Mol Sci. 2020 Apr 13;21(8):2692. doi: 10.3390/ijms21082692.


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.

Keywords: TNFα metabolic pathway; apoptosis; auditory brain response; cochlea; electrophysiological threshold; in vivo siRNA administration; synaptopathy.

MeSH terms

  • Animals
  • Auditory Threshold
  • Biomarkers
  • Disease Models, Animal
  • Disease Susceptibility
  • Evoked Potentials, Auditory, Brain Stem
  • Fluorescent Antibody Technique
  • Gene Expression Profiling
  • Gene Expression Regulation
  • Gene Silencing*
  • Hearing Loss, Noise-Induced / diagnosis
  • Hearing Loss, Noise-Induced / genetics*
  • Hearing Loss, Noise-Induced / metabolism*
  • RNA Interference
  • RNA, Small Interfering / genetics
  • Rats
  • Tumor Necrosis Factor-alpha / genetics*
  • Tumor Necrosis Factor-alpha / metabolism*


  • Biomarkers
  • RNA, Small Interfering
  • Tumor Necrosis Factor-alpha