Low-dose D-methionine and N-acetyl-L-cysteine for protection from permanent noise-induced hearing loss in chinchillas

• Published in: Otolaryngology-head and neck surgery Vol. 145; no. 6; p. 999
• Main Authors: Clifford, Royce E, Coleman, John K M, Balough, Ben J, Liu, Jianzhong, Kopke, Richard D, Jackson, Ronald L
• Format: Journal Article
• Language: English
• Published: England 01.12.2011
• Subjects: 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; Hearing Loss, Noise-Induced - prevention & control; Injections, Intraperitoneal; Methionine - administration & dosage; Random Allocation; Reference Values; Treatment Outcome
• ISSN: 1097-6817
• DOI: 10.1177/0194599811414496

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. 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. Laboratory. 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. 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). 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.