{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,31]],"date-time":"2026-07-31T16:26:43Z","timestamp":1785515203237,"version":"3.56.0"},"reference-count":36,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T00:00:00Z","timestamp":1658448000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"the Basic Science Research Program through the National Research Foundation of Korea (NRF)","award":["2022R1I1A1A01069681"],"award-info":[{"award-number":["2022R1I1A1A01069681"]}]},{"name":"the Ministry of Education","award":["2022R1I1A1A01069681"],"award-info":[{"award-number":["2022R1I1A1A01069681"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antioxidants"],"abstract":"<jats:p>Alpha-lipoic acid (ALA) is an antioxidant with oto-protective effects. In the present study, the safety and effectiveness of ALA therapy after noise-induced hearing loss was confirmed based on the administration method. The safety of intratympanic ALA (IT-ALA) was evaluated with oto-endoscopy and middle ear mucosa morphologic study. Perilymph ALA concentrations according to the administration routes were compared, and the efficacy of ALA was investigated through hearing tests and cochlear histological studies. The middle ear mucosa was swollen 1 week after IT-ALA but completely recovered within 3 weeks. ALA concentration in the perilymph was significantly higher in the IT-ALA group. Recovery of organ of Corti morphology and hearing levels were predominant in the IT-ALA group compared with the intraperitoneal injection group (IP-ALA) and showed similar rescue effects in the IT-dexamethasone group (IT-DEX). Interleukin-1 beta and nuclear factor-kappa B expression was significantly downregulated in the IT-ALA group. IT-ALA showed better cochlear recovery from acoustic trauma with higher inner ear penetration rate than IP-ALA. The rescue effect of IT-ALA after noise-induced hearing loss was similar to IT-DEX; however, the ALA and DEX mechanisms are different. IT-ALA appears to be another safe and effective treatment modality after acoustic trauma and comparable to IT-DEX.<\/jats:p>","DOI":"10.3390\/antiox11081423","type":"journal-article","created":{"date-parts":[[2022,7,22]],"date-time":"2022-07-22T12:53:45Z","timestamp":1658494425000},"page":"1423","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7728-1232","authenticated-orcid":false,"given":"Jae Sang","family":"Han","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ye Lin","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hyo Jeong","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Biomedicine & Health Sciences, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Mee","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Gangneung Asan Hospital, College of Medicine University of Ulsan, 38 Bangdong-gil, Sacheon-myeon, Gangneung-si 25440, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3127-5827","authenticated-orcid":false,"given":"Yeonji","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"So Young","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Yeouido St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 10, 63-ro, Yeongdeungpo-gu, Seoul 07345, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shi Nae","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology-Head and Neck Surgery, Seoul St. Mary\u2019s Hospital, College of Medicine, The Catholic University of Korea, 222, Banpo-daero, Seocho-gu, Seoul 06591, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,7,22]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1016\/S0026-0495(00)80077-3","article-title":"What is oxidative stress?","volume":"49","author":"Betteridge","year":"2000","journal-title":"Metabolism"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"8416763","DOI":"10.1155\/2017\/8416763","article-title":"Oxidative Stress: Harms and Benefits for Human Health","volume":"2017","author":"Pizzino","year":"2017","journal-title":"Oxid. Med. Cell. Longev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"3591","DOI":"10.2174\/092986710792927895","article-title":"Oxidative Stress in the Cochlea: An Update","volume":"17","author":"Poirrier","year":"2010","journal-title":"Curr. Med. Chem."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1007\/s00405-011-1671-2","article-title":"Unbalanced oxidative status in idiopathic sudden sensorineural hearing loss","volume":"269","author":"Capaccio","year":"2012","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Pak, J.H., Kim, Y., Yi, J., and Chung, J.W. (2020). Antioxidant Therapy against Oxidative Damage of the Inner Ear: Protection and Preconditioning. Antioxidants, 9.","DOI":"10.3390\/antiox9111076"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/S0306-3623(96)00474-0","article-title":"The pharmacology of the antioxidant lipoic acid","volume":"29","author":"Biewenga","year":"1997","journal-title":"Gen. Pharmacol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"51","DOI":"10.3109\/00207454.2010.535934","article-title":"The contributions of antioxidant activity of lipoic acid in reducing neurogenerative progression of Parkinson\u2019s disease: A review","volume":"121","author":"Cavalcanti","year":"2011","journal-title":"Int. J. Neurosci."},{"key":"ref_8","first-page":"e12773","article-title":"The Effect of Alpha-Lipoic Acid on Diabetic Peripheral Neuropathy and the Upcoming Depressive Disorders of Type II Diabetics","volume":"13","author":"Karalis","year":"2021","journal-title":"Cureus"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1159\/000448666","article-title":"Lipoic Acid in the Prevention of Acute Kidney Injury","volume":"134","author":"Zhang","year":"2016","journal-title":"Nephron"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1038\/s41419-018-0888-z","article-title":"Evaluating protective and therapeutic effects of alpha-lipoic acid on cisplatin-induced ototoxicity","volume":"9","author":"Kim","year":"2018","journal-title":"Cell. Death Dis."},{"key":"ref_11","first-page":"2793","article-title":"Mechanism of alpha-lipoic acid in attenuating kanamycin-induced ototoxicity","volume":"7","author":"Wang","year":"2012","journal-title":"Neural. Regen. Res."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"e648","DOI":"10.1097\/MAO.0000000000002643","article-title":"Otoprotective Effects of \u03b1-lipoic Acid on A\/J Mice With Age-related Hearing Loss","volume":"41","author":"Huang","year":"2020","journal-title":"Otol. Neurotol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/j.ejphar.2017.01.042","article-title":"The effect of systemic lipoic acid on hearing preservation after cochlear implantation via the round window approach: A guinea pig model","volume":"799","author":"Chang","year":"2017","journal-title":"Eur. J. Pharmacol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"102329","DOI":"10.1016\/j.nano.2020.102329","article-title":"Intratympanic administration of alpha-lipoic acid-loaded pluronic F-127 nanoparticles ameliorates acute hearing loss","volume":"32","author":"Jung","year":"2021","journal-title":"Nanomedicine"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1515","DOI":"10.1097\/SCS.0000000000000881","article-title":"Evaluation of the protective effect of \u03b1-lipoic acid on cisplatin ototoxicity using distortion-product otoacoustic emission measurements: An experimental animal study","volume":"25","author":"Ozkul","year":"2014","journal-title":"J. Craniofac. Surg."},{"key":"ref_16","first-page":"1034","article-title":"Comparison of the antioxidants lipoic acid pharmacokinetics in inner ear between intravenous and intratympanic administration in guinea pigs","volume":"44","author":"Zhou","year":"2009","journal-title":"Zhonghua Er Bi Yan Hou Tou Jing Wai Ke Za Zhi"},{"key":"ref_17","unstructured":"de Cates, C., Winters, R., and Intratympanic Steroid Injection (2022, July 20). [Updated 9 January 2022]. StatPearls [Internet], Available online: https:\/\/www.ncbi.nlm.nih.gov\/books\/NBK567708\/."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"226","DOI":"10.3389\/fncel.2020.00226","article-title":"Antioxidants and Vasodilators for the Treatment of Noise-Induced Hearing Loss: Are They Really Effective?","volume":"14","author":"Alvarado","year":"2020","journal-title":"Front. Cell. Neurosci."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1016\/S0378-5955(03)00067-4","article-title":"Noise-induced hearing loss in chinchillas pre-treated with glutathione monoethylester and R-PIA","volume":"179","author":"Hight","year":"2003","journal-title":"Hear. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"138","DOI":"10.1016\/S0378-5955(00)00176-3","article-title":"Reduction of noise-induced hearing loss using L-NAC and salicylate in the chinchilla","volume":"149","author":"Kopke","year":"2000","journal-title":"Hear. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"989","DOI":"10.1016\/j.sjbs.2018.08.008","article-title":"Effects of \u03b1 lipoic acid on noise induced oxidative stress in rats","volume":"26","year":"2019","journal-title":"Saudi. J. Biol. Sci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"25","DOI":"10.4137\/CMENT.S10711","article-title":"Comparison of the Protective Effects of Radix Astragali, \u03b1-Lipoic Acid, and Vitamin E on Acute Acoustic Trauma","volume":"5","author":"Xiong","year":"2012","journal-title":"Clin. Med. Insights Ear Nose Throat"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1097\/MAO.0000000000000759","article-title":"Therapeutic Effect of Dexamethasone for Noise-induced Hearing Loss: Systemic Versus Intratympanic Injection in Mice","volume":"36","author":"Han","year":"2015","journal-title":"Otol. Neurotol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1016\/S0378-5955(97)00133-0","article-title":"Cochlear pathology induced by aminoglycoside ototoxicity during postnatal maturation in cats","volume":"113","author":"Leake","year":"1997","journal-title":"Hear. Res."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.anl.2011.11.008","article-title":"Comparison of functional and morphologic characteristics of mice models of noise-induced hearing loss","volume":"40","author":"Park","year":"2013","journal-title":"Auris Nasus Larynx"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1080\/00016480252814153","article-title":"Induction of mucous cell metaplasia in the middle ear of rats using a three-step method: An improved model for otitis media with mucoid effusion","volume":"122","author":"Tsuboi","year":"2002","journal-title":"Acta Otolaryngol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.bbrc.2014.04.118","article-title":"Alpha-lipoic acid protects against cisplatin-induced ototoxicity via the regulation of MAPKs and proinflammatory cytokines","volume":"449","author":"Kim","year":"2014","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"111555","DOI":"10.1016\/j.fct.2020.111555","article-title":"Anti-oxidant and anti-inflammatory effects of caffeic acid: In vivo evidences in a model of noise-induced hearing loss","volume":"143","author":"Paciello","year":"2020","journal-title":"Food Chem. Toxicol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Paciello, F., Pisani, A., Rolesi, R., Escarrat, V., Galli, J., Paludetti, G., Grassi, C., Troiani, D., and Fetoni, A.R. (2021). Noise-Induced Cochlear Damage Involves PPAR Down-Regulation through the Interplay between Oxidative Stress and Inflammation. Antioxidants, 10.","DOI":"10.3390\/antiox10081188"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.ijporl.2016.10.008","article-title":"Comparison of the effects of lipoic acid and glutathione against cisplatin-induced ototoxicity in auditory cells","volume":"91","author":"Koo","year":"2016","journal-title":"Int. J. Pediatric Otorhinolaryngol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"100783","DOI":"10.1016\/j.ymgmr.2021.100783","article-title":"Protective effects of alpha-lipoic acid on hair cell damage in diabetic zebrafish model","volume":"28","author":"Kim","year":"2021","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1301","DOI":"10.1007\/s00405-016-4301-1","article-title":"A comprehensive study of oxidative stress in sudden hearing loss","volume":"274","author":"Gul","year":"2017","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1007\/s00418-016-1436-5","article-title":"Characterisation of cochlear inflammation in mice following acute and chronic noise exposure","volume":"146","author":"Tan","year":"2016","journal-title":"Histochem. Cell. Biol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2271","DOI":"10.1007\/s00405-015-3689-3","article-title":"Intratympanic corticosteroids injections: A systematic review of literature","volume":"273","author":"Lavigne","year":"2016","journal-title":"Eur. Arch. Otorhinolaryngol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1097\/MAO.0000000000000725","article-title":"Intratympanic Steroid Treatments May Improve Hearing via Ion Homeostasis Alterations and Not Immune Suppression","volume":"36","author":"MacArthur","year":"2015","journal-title":"Otol. Neurotol. Off. Publ. Am. Otol. Soc. Am. Neurotol. Soc. Eur. Acad. Otol. Neurotol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1870","DOI":"10.4049\/jimmunol.1002275","article-title":"IL-1\u03b2 is overexpressed and aberrantly regulated in corticosteroid nonresponders with autoimmune inner ear disease","volume":"186","author":"Pathak","year":"2011","journal-title":"J. Immunol."}],"container-title":["Antioxidants"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1423\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T23:55:02Z","timestamp":1760140502000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-3921\/11\/8\/1423"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,7,22]]},"references-count":36,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2022,8]]}},"alternative-id":["antiox11081423"],"URL":"https:\/\/doi.org\/10.3390\/antiox11081423","relation":{},"ISSN":["2076-3921"],"issn-type":[{"value":"2076-3921","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,7,22]]}}}