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.