Dextromethorphan Attenuates Sensorineural Hearing Loss in an Animal Model and Population-Based Cohort Study

• Main Authors: Hsin-Chien Chen, Chih-Hung Wang, Wu-Chien Chien, Chi-Hsiang Chung, Cheng-Ping Shih, Yi-Chun Lin, I-Hsun Li, Yuan-Yung Lin, Chao-Yin Kuo
• Format: Article
• Language: English
• Published: MDPI AG 2020-08-01
• Series: International Journal of Environmental Research and Public Health
• Subjects: dextromethorphan; noise; hearing loss; cochlea; synapse
• Online Access: https://www.mdpi.com/1660-4601/17/17/6336
• ISSN: 1661-7827; 1660-4601

The effect of dextromethorphan (DXM) use in sensorineural hearing loss (SNHL) has not been fully examined. We conducted an animal model and nationwide retrospective matched-cohort study to explore the association between DXM use and SNHL. Eight-week-old CBA/CaJ hearing loss was induced by a white noise 118 dB sound pressure level for 3 h. DXM (30 mg/kg) was administered intraperitoneally for 5 days and boost once round window DXM socking. In population-based study, we examined the medical records over 40 years old in Taiwan’s National Health Insurance Research Database between 2000 and 2015 to establish retrospective matched-cohort to explore the correlation between DXM use and SNHL. Using click auditory brainstem response (ABR), hearing threshold was measured as 48.6 ± 2.9 dB in control mice compared with 42.6 ± 7.0 dB in DXM mice, which differed significantly (<i>p</i> = 0.002) on day 60 after noise exposure with a larger ABR wave I amplitude in DXM mice. In human study, we used a Cox regression hazard model to indicate that a significantly lower percentage individuals developed SNHL compared with and without DXM use (0.44%, 175/39,895 vs. 1.05%, 1675/159,580, <i>p</i> < 0.001). After adjustment for age and other variables [adjusted hazard ratio: 0.725 (95% confidence interval: 0.624–0.803, <i>p</i> < 0.001)], this study also demonstrated that DXM use appeared to reduce the risk of developing SNHL. This animal study demonstrated that DXM significantly attenuated noise-induced hearing loss. In human study, DXM use may have a protective effect against SNHL.