title: Low-dose D-methionine and N-acetyl-L-cysteine for protection from permanent noise-induced hearing loss in chinchillas.
abstract: OBJECTIVE
  Despite efforts at public health awareness and stringent industrial standards for hearing protection, noise-induced hearing loss (NIHL) remains a formidable public health concern. Although many antioxidants have proven to be beneficial in the laboratory for prevention of permanent NIHL, low-dose combinations of compounds with different biochemical mechanisms of action may allow long-term administration with fewer side effects and equal efficacy. The mixture of D-methionine and N-acetyl-L-cysteine administered at levels less than 10% of standard dosing has not been previously reported.
  
  
  METHODS
  Twenty-six female adult Chinchilla laniger were placed in 4 study groups, consisting of (1) a group receiving combination 12.5 mg/kg each D-methionine and N-acetyl-L-cysteine (DMET/NAC group), (2) a group receiving 12.5 mg/kg D-methionine (DMET-only group), (3) a group receiving 12.5 mg/kg N-acetyl-L-cysteine (NAC-only group), and (4) saline controls.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  All groups received twice-daily intraperitoneal injections 2 days prior to noise exposure, 1 hour before and after exposure on day 3, and for 2 days subsequently, totaling 10 doses of 125 mg/kg for each antioxidant over 5 days.
  
  
  RESULTS
  Although NAC-only animals paralleled saline control recovery during 3 weeks, the DMET-only group revealed gradual improvement with statistically significant recovery in the middle frequencies. The DMET/NAC group showed significant improvement at most frequencies compared with controls (P < .001 and P < .05).
  
  
  CONCLUSIONS
  Significant recovery of hearing was observed following continuous noise exposure with either DMET only or a combination of low-dose DMET/NAC, demonstrating a considerably lower dose of antioxidants required than previously reported for hearing recovery following acoustic trauma.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Naval Medical Center, San Diego, California 92134-5000, USA. royce.clifford@usmc.mil
authors.forename: Royce E
authors.initials: RE
authors.lastname: Clifford
authors.forename: John K M
authors.initials: JK
authors.lastname: Coleman
authors.forename: Ben J
authors.initials: BJ
authors.lastname: Balough
authors.forename: Jianzhong
authors.initials: J
authors.lastname: Liu
authors.forename: Richard D
authors.initials: RD
authors.lastname: Kopke
authors.forename: Ronald L
authors.initials: RL
authors.lastname: Jackson
mesh_terms: D000111:Acetylcysteine / Q000008:administration & dosage*; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002682:Chinchilla; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D005260:Female; D006317:Hearing Loss, Noise-Induced / Q000188:drug therapy* / Q000517:prevention & control; D007274:Injections, Intraperitoneal; D008715:Methionine / Q000008:administration & dosage*; D011897:Random Allocation; D012016:Reference Values; D016896:Treatment Outcome
chemical_list: D008715:Methionine; D000111:Acetylcysteine