Functional and biochemical protection by combined N-acetylcysteine and D-methionine in guinea pig noise-induced hearing loss.

PURPOSE: This study examined whether combining antioxidants could enhance protection and permit lower dosing for treating noise-induced hearing loss (NIHL). The therapeutic effects of D-methionine (DMET) and N-acetylcysteine (NAC) were evaluated in a guinea pig model.

METHODS

Ninety-six guinea pigs were randomly assigned to eight groups: control, saline, three NAC-only groups (100, 150, 200 mg/kg), and three NAC + DMET groups (100, 200, 400 mg/kg). One hour after six hours of broadband noise exposure, treatments were administered intraperitoneally every 12 h for seven days. Auditory brainstem responses (ABR) were measured before exposure and on day 14. Cochlear tissues were analyzed for Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities and lipid peroxidation (LPO) levels.

RESULTS

No significant body weight differences were observed between saline and treated groups. NAC alone and in combination with DMET improved ABR thresholds in a dose-dependent manner. The combined NAC (200 mg/kg) + DMET (400 mg/kg) group achieved complete ABR recovery. Noise-induced reductions in ATPase activities were dose-dependently reversed by both treatments. The highest-dose combination restored 87.3% of Na⁺/K⁺-ATPase and 94.7% of Ca²⁺-ATPase activity compared to controls. LPO levels declined with increasing NAC doses, with NAC 200 mg/kg alone showing the greatest reduction.

CONCLUSIONS

Combined NAC (200 mg/kg) and DMET (400 mg/kg) yielded the most substantial functional protection against NIHL. This combination was accompanied by lower LPO levels and higher Na⁺/K⁺-ATPase and Ca²⁺-ATPase activities in the cochlear lateral wall, indicating a potential role in maintaining cochlear homeostasis following acoustic injury.