Effects of delayed and extended antioxidant treatment on acute acoustic trauma

Free Radic Res. 2011 Oct;45(10):1162-72. doi: 10.3109/10715762.2011.605360. Epub 2011 Aug 10.


Objective: Hair cell death caused by acute acoustic trauma (AAT) reaches a secondary maximum at 7-10 days after noise exposure due to a second oxidative stress. Therefore, this study tested the effects of a combination of hydroxylated alpha-phenyl-tert-butylnitrone (4-OHPBN), N-acetyl-L-cysteine (NAC) and acetyl-L-carnitine (ALCAR) on AAT when the duration of treatment was extended over the period of 7-10 days after noise exposure as well as when the initial treatment was delayed 24 to 48 h after noise exposure.

Methods: Thirty chinchilla were exposed to a 105 dB octave-band noise centred at 4 kHz for 6 h and received the following treatments: (1) noise + saline (2-5) 4-OHPBN (20 mg/kg) + NAC (50 mg/kg) + ALCAR (20 mg/kg) intraperitoneally injected beginning 24 or 48 h after noise exposure twice daily for the next 2, 8 or 9 days. Auditory brainstem response (ABR) threshold shifts, outer hair cell (OHC) counts and organ of Corti immunohistochemistry were analyzed.

Results: The combination administration decreased ABR threshold shifts, inhibited OHC loss and reduced 4-hydroxynonenal (4-HNE) immunostaining. Significant decreases in the threshold shifts and reduction in OHC loss were observed with a shorter delay before starting treatment (24 h) and longer duration (9 days) treatment.

Conclusions: These results demonstrate that the administration of antioxidant drugs extended up to 10 days after noise exposure can effectively treat AAT in a chinchilla model. This may provide significant and potentially clinically important information about the effective therapeutic window for AAT treatment.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Acoustic Stimulation
  • Animals
  • Antioxidants / administration & dosage*
  • Chinchilla
  • Drug Administration Schedule
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Female
  • Hair Cells, Auditory, Outer / drug effects
  • Hair Cells, Auditory, Outer / metabolism
  • Hair Cells, Auditory, Outer / pathology
  • Hearing Loss, Noise-Induced / drug therapy*
  • Hearing Loss, Noise-Induced / metabolism
  • Hearing Loss, Noise-Induced / pathology
  • Immunohistochemistry
  • Noise / adverse effects
  • Oxidative Stress / physiology


  • Antioxidants