The therapeutic effect and underlying biochemical mechanism of methylprednisolone and D-methionine in "rescuing" noise-induced hearing loss in guinea pigs

Objectives: Currently, there are no approved therapeutics for noise-induced hearing loss (NIHL). Both oxidative stress and cochlear inflammation play important roles in the mechanism of NIHL. In this study, we evaluate the effect of D-methionine (D-met) and methylprednisolone (MP) on noise-induced hearing loss of guinea pigs.

Design: One hundred and thirty-two male guinea pigs were evenly divided into eleven groups: control, saline, MP (15, 30, 45 mg/kg), D-met (200, 400, 600 mg/kg), and combinations of MP (15, 30, 45 mg/kg) with D-met (200, 400, 600 mg/kg) in increasing doses. Sixty minutes following a 6-hour exposure to continuous broadband white noise at a sound pressure level of 105 ± 2 dB, treatments were given every 12 h over the course of 3 days. Click-evoked auditory brainstem responses were evaluated one day before and fourteen days after noise exposure. The animals in the combination group were sacrificed 14 days after noise exposure, and cochlear lateral wall Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities, and lipid peroxidation (LPO) were evaluated.

Results: The mean permanent threshold shift (PTS) showed a dose-dependent rescue effect from low to high doses in both MP and D-met treatment groups. In the combination treatment groups, MP (45 mg/kg) with D-met (600 mg/kg) demonstrated a complete rescue response without a significant difference in PTS compared to the control group. The noise-induced decreases in Na⁺, K⁺-ATPase and Ca²⁺-ATPase activities demonstrated dose-dependent recoveries from the low to high dose combination groups. Specifically, the MP (45 mg/kg) with D-met (600 mg/kg) group achieved 84.8% and 95.5% recovery of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels, respectively, compared to the control group. The noise-induced increase in LPO levels exhibited dose-dependent alleviation from the low to high dose combination groups, showing only a 12.3% LPO increment in the MP (45 mg/kg) with D-met (600 mg/kg) group.

Conclusions: Noise-induced hearing loss was completely rescued in the MP (45 mg/kg) with D-met (600 mg/kg) treatment group. Significant decreases in cochlear lateral wall oxidative stress were demonstrated, along with the reversal of Na⁺, K⁺-ATPase and Ca²⁺-ATPase activity levels.