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

• Published in: Hearing research 2024-12, Vol.454, p.109148, Article 109148
• Main Authors: Wu, Po-Hsuan, Lo, Wu-Chia, Chang, Chih-Ming, Cheng, Po-Wen, Liu, Shing-Hwa
• Format: Article
• Language: English
• Subjects: Acoustic Stimulation; Animals; Auditory brainstem response; Auditory Threshold - drug effects; Cochlea - drug effects; Cochlea - metabolism; Cochlea - physiopathology; D-methionine; Disease Models, Animal; Dose-Response Relationship, Drug; Drug Therapy, Combination; Evoked Potentials, Auditory, Brain Stem - drug effects; Guinea Pigs; Hearing - drug effects; Hearing Loss, Noise-Induced - drug therapy; Hearing Loss, Noise-Induced - metabolism; Hearing Loss, Noise-Induced - physiopathology; Lipid peroxidation; Lipid Peroxidation - drug effects; Male; Methionine - administration & dosage; Methylprednisolone; Methylprednisolone - administration & dosage; Methylprednisolone - pharmacology; Noise; Noise - adverse effects; Oxidative Stress - drug effects; Sodium-Potassium-Exchanging ATPase - metabolism; Time Factors
• ISSN: 0378-5955; 1878-5891; 1878-5891
• DOI: 10.1016/j.heares.2024.109148

•Lipid peroxidation is prominent in the cochlear lateral wall of guinea pigs after noise exposure.•Both Na+, K+-ATPase and Ca2+-ATPase activities in the cochlear lateral wall decreased after noise exposure.•Oxidative stress in the cochlear lateral wall is relieved after the combined use of methylprednisolone and D-methionine.•The combined use of methylprednisolone and D-methionine restored the hearing threshold and the activities of both Na+, K+-ATPase and Ca2+-ATPase in the cochlear lateral wall of guinea pigs. 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. 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. 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. Noise-induced hearing loss was completely re