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.

STUDY DESIGN:

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.

SETTING:

Laboratory.

SUBJECTS AND 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).

CONCLUSION:

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: Royce E Clifford, John K M Coleman, Ben J Balough, Jianzhong Liu, Richard D Kopke, Ronald L Jackson
• Journal: Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery (Otolaryngol Head Neck Surg) Vol. 145 Issue 6 Pg. 999-1006 (Dec 2011) ISSN: 1097-6817 [Electronic] England
• PMID: 21750343 (Publication Type: Comparative Study, Journal Article, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Methionine
• Acetylcysteine

Topics

• Acetylcysteine (administration & dosage)
• Animals
• Auditory Threshold (drug effects)
• Chinchilla
• Disease Models, Animal
• Dose-Response Relationship, Drug
• Drug Administration Schedule
• Drug Therapy, Combination
• Evoked Potentials, Auditory, Brain Stem (drug effects)
• Female
• Hearing Loss, Noise-Induced (drug therapy, prevention & control)
• Injections, Intraperitoneal
• Methionine (administration & dosage)
• Random Allocation
• Reference Values
• Treatment Outcome