title: Effects of delayed and extended antioxidant treatment on acute acoustic trauma.
abstract: 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.
authors.affiliation: Audiology & Speech-Language Pathology & Research Institute of Biomimetic Sensory Control, College of Medical Sciences, Catholic University of Daegu, Kyungsansi, South Korea. cchoi@cu.ac.kr
authors.forename: Chul-Hee
authors.initials: CH
authors.lastname: Choi
authors.forename: Kejian
authors.initials: K
authors.lastname: Chen
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Du
authors.forename: Robert A
authors.initials: RA
authors.lastname: Floyd
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
mesh_terms: D000161:Acoustic Stimulation; D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D002682:Chinchilla; D004334:Drug Administration Schedule; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D018072:Hair Cells, Auditory, Outer / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D007150:Immunohistochemistry; D009622:Noise / Q000009:adverse effects; D018384:Oxidative Stress / Q000502:physiology
chemical_list: D000975:Antioxidants