title: An experimental comparative study of dexamethasone, melatonin and tacrolimus in noise-induced hearing loss.
abstract: CONCLUSIONS
  The calcineurin inhibitor tacrolimus (TCR) and the pineal gland hormone and antioxidant melatonin (MLT) have been shown to possess otoprotective properties against noise-induced hearing loss (NIHL). In contrast, dexamethasone (DXM) was not effective as an otoprotective agent against NIHL. Further studies are needed to understand the exact molecular mechanisms involved.
  
  
  OBJECTIVE
  Exposure to noise pollution and use of audio devices for long periods of time at high volume is known to cause hearing loss or NIHL. Our goal was to evaluate the effectiveness of various known compounds such as the anti-inflammatory DXM, the antioxidant MLT and the immunosuppressant TCR against NIHL.
  
  
  METHODS
  Thirty-two Wistar rats were randomly divided into groups that were then exposed to intense white noise at 120 dB SPL for 4 h. The day before and for a period of 14 days, test groups were administered one of the three compounds. The efficacy of the compounds against NIHL was determined after examining the shifts in the levels of distortion product otoacoustic emissions (DPOAEs) and changes in the threshold of auditory brainstem responses (ABRs). Cytocochleograms and determination of gene expression in whole rat cochlea were carried out at day 21.
  
  
  RESULTS
  Treatment with DXM had no otoprotective effect, while animals treated with MLT experienced an improvement in their hearing functionality. This effect, which is probably linked to MLT's ability to reduce c-fos and TNF-alpha gene expression thereby preventing outer hair cell (OHC) loss, was even more pronounced in week 3. For its part, TCR provided protection against injury to the cochlea from week 1, eventually leading to a full recovery in hearing. The compound reduced both c-fos and TNF-alpha expression, as well as OHC loss.
authors.affiliation: Hospital Clinico Universitario Research Foundation, Valencia, Spain.
authors.forename: Esperanza
authors.initials: E
authors.lastname: Bas
authors.forename: Francisco
authors.initials: F
authors.lastname: Martinez-Soriano
authors.forename: José M
authors.initials: JM
authors.lastname: Láinez
authors.forename: Jaime
authors.initials: J
authors.lastname: Marco
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D000975:Antioxidants / Q000627:therapeutic use*; D003907:Dexamethasone / Q000627:therapeutic use*; D016057:Evoked Potentials, Auditory, Brain Stem; D018072:Hair Cells, Auditory, Outer / Q000502:physiology; D006317:Hearing Loss, Noise-Induced / Q000503:physiopathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D008297:Male; D008550:Melatonin / Q000627:therapeutic use*; D017084:Otoacoustic Emissions, Spontaneous; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016559:Tacrolimus / Q000627:therapeutic use*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D000975:Antioxidants; D007166:Immunosuppressive Agents; D016760:Proto-Oncogene Proteins c-fos; D014409:Tumor Necrosis Factor-alpha; D003907:Dexamethasone; D008550:Melatonin; D016559:Tacrolimus