{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:03:48Z","timestamp":1792091028556,"version":"4.4.0"},"reference-count":54,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T00:00:00Z","timestamp":1731369600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The Laryngoscope"],"published-print":{"date-parts":[[2025,4]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>A feared complication of aminoglycoside treatment is ototoxicity, which is theorized to be attributed to the production of aminoglycoside\u2010induced reactive oxygen species. Previous studies using animal models have suggested that numerous therapies targeting reducing oxidative stress may prevent ototoxicity from aminoglycosides. However, few clinical studies have been conducted on these antioxidants. This systematic review and meta\u2010analysis examines the effectiveness of antioxidant therapies in the treatment of aminoglycoside\u2010induced ototoxicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Data Sources<\/jats:title><jats:p>PubMed, Embase, Web of Science, and <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/clinicaltrials.gov\">ClinicalTrials.gov<\/jats:ext-link>.<\/jats:p><\/jats:sec><jats:sec><jats:title>Review Method<\/jats:title><jats:p>A literature search was conducted in August 2024. This review sought randomized controlled trials to be conducted on humans to examining otologic outcomes in aminoglycoside\u2010induced ototoxicity following administration of medications intended to reduce oxidative stress.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A systematic review yielded 2037 results, of which seven studies met inclusion criteria. N\u2010acetylcysteine (NAC) was investigated in four studies, aspirin in two studies, and vitamin E in one study. Six studies examined the benefit of antioxidant treatments for up to 8\u2009weeks after administration while one study tested subjects' hearing after 1\u2009year. In pooled analysis, two studies assessing NAC showed the greatest reduction in ototoxicity (RR 0.112, 95% CI, 0.032\u20130.395; <jats:italic>p<\/jats:italic>\u2009=\u20090.0007; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u200918%), followed by two studies examining aspirin (RR 0.229, 95% CI, 0.080\u20130.650; <jats:italic>p<\/jats:italic>\u2009=\u20090.0057; <jats:italic>I<\/jats:italic><jats:sup>2<\/jats:sup>\u2009=\u20090%). One study performed with vitamin E did not find a reduction in ototoxicity compared to the placebo (RR 0.841, 95% CI, 0.153\u20134.617; <jats:italic>p<\/jats:italic>\u2009=\u20090.8416).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Multiple studies have shown that NAC and aspirin are effective in reducing ototoxicity from treatment with aminoglycosides. However, there is a lack of high\u2010quality evidence. Additional studies should examine whether aspirin and N\u2010acetylcysteine provide long\u2010term benefit, and which of the other promising antioxidants translate from animal models.<\/jats:p><\/jats:sec><jats:sec><jats:title>Level of Evidence<\/jats:title><jats:p>NA <jats:italic>Laryngoscope<\/jats:italic>, 135:1278\u20131286, 2025<\/jats:p><\/jats:sec>","DOI":"10.1002\/lary.31902","type":"journal-article","created":{"date-parts":[[2024,11,12]],"date-time":"2024-11-12T10:24:03Z","timestamp":1731407043000},"page":"1278-1286","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Antioxidant Therapies in the Treatment of Aminoglycoside\u2010Induced Ototoxicity: A Meta\u2010Analysis"],"prefix":"10.1002","volume":"135","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-6160-9328","authenticated-orcid":false,"given":"Patrick J.","family":"Gaffney","sequence":"first","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunal R.","family":"Shetty","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sancak","family":"Yuksel","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vivian F.","family":"Kaul","sequence":"additional","affiliation":[{"name":"Department of Otorhinolaryngology \u2013 Head and Neck Surgery The University of Texas Health Science Center at Houston  Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,11,12]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1128\/ecosalplus.ESP-0002-2018"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkn469"},{"key":"e_1_2_6_4_1","volume-title":"Aminoglycosides","author":"Block M","year":"2023"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/937861"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox12071316"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24087596"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.5152\/iao.2015.650"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jat.3043"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(83)90030-8"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.2165\/00002018-199309020-00006"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1023\/a:1006934612368"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495-006-0580-0"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuro.2022.10.013"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480310001484"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bjorl.2017.07.011"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11356-023-26164-5"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016489.2023.2220365"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12603-011-0119-0"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.l4898"},{"key":"e_1_2_6_21_1","unstructured":"EpsteinR FonnesbeckC WilliamsonE et al.Psychosocial and Pharmacologic Interventions for Disruptive Behavior in Children and Adolescents [Internet]. 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