{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,24]],"date-time":"2026-02-24T07:59:57Z","timestamp":1771919997738,"version":"3.50.1"},"reference-count":38,"publisher":"MDPI AG","issue":"2","license":[{"start":{"date-parts":[[2026,2,21]],"date-time":"2026-02-21T00:00:00Z","timestamp":1771632000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Education","award":["RS-2022-NR075243"],"award-info":[{"award-number":["RS-2022-NR075243"]}]},{"name":"Ministry of Education","award":["RS-2024-00340841"],"award-info":[{"award-number":["RS-2024-00340841"]}]},{"DOI":"10.13039\/501100003725","name":"Catholic Medical Center Research Foundation","doi-asserted-by":"publisher","award":["RS-2022-NR075243 and RS-2024-00340841"],"award-info":[{"award-number":["RS-2022-NR075243 and RS-2024-00340841"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>This study evaluates the protective effects of alpha-lipoic acid (ALA), diltiazem (DIL), and N-acetylcysteine (NAC) as potential adjunctive agents to enhance intratympanic dexamethasone (IT-DEX) therapy in noise-induced hearing loss. A two-phase experiment using C57BL\/6J mice was conducted. In phase 1, candidate drugs were screened by perilymph concentration analysis using ultra-high-performance liquid chromatography, auditory brainstem response (ABR) threshold, and organ of Corti (OC) morphology. Western blot analysis evaluated inflammatory markers. Phase 2 investigated the synergistic effects of co-administration of the most promising candidates with DEX. All drugs successfully penetrated the inner ear via IT injection. In the noise-induced hearing loss model, ALA and DIL individually demonstrated significant improvements in ABR thresholds and OC morphology compared to DEX alone, while NAC showed no therapeutic benefit. Western blot analysis revealed that ALA and DIL suppressed inflammatory markers through distinct antioxidant-mediated mechanisms, contrasting with DEX\u2019s anti-inflammatory pathway. However, combination therapy with DEX + ALA or DEX + DIL increased middle ear inflammation and failed to produce synergistic therapeutic effects. While ALA and DIL showed individual therapeutic promise through complementary mechanisms, combination with DEX did not enhance efficacy, suggesting that simple drug combinations may not translate to improved IT therapy outcomes.<\/jats:p>","DOI":"10.3390\/antiox15020268","type":"journal-article","created":{"date-parts":[[2026,2,23]],"date-time":"2026-02-23T10:00:52Z","timestamp":1771840852000},"page":"268","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Evaluation of Intratympanic Alpha-Lipoic Acid and Diltiazem as Alternatives to Dexamethasone in Noise-Induced Hearing Loss in a Murine Model"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-1232","authenticated-orcid":false,"given":"Jae Sang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kyusun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ye Lin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"},{"name":"Department of Medical Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji Hyung","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"So Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shi Nae","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology\u2014Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2377","DOI":"10.1002\/lary.31194","article-title":"The Breakdown of Blood-Labyrinth Barrier Makes it Easier for Drugs to Enter the Inner Ear","volume":"134","author":"Ke","year":"2024","journal-title":"Laryngoscope"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.heares.2017.12.010","article-title":"Communication pathways to and from the inner ear and their contributions to drug delivery","volume":"362","author":"Salt","year":"2018","journal-title":"Hear. 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