{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,26]],"date-time":"2026-02-26T15:12:49Z","timestamp":1772118769868,"version":"3.50.1"},"reference-count":21,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T00:00:00Z","timestamp":1715904000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005380","name":"American Neurotology Society","doi-asserted-by":"publisher","award":["2021\u20102"],"award-info":[{"award-number":["2021\u20102"]}],"id":[{"id":"10.13039\/100005380","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000055","name":"National Institute on Deafness and Other Communication Disorders","doi-asserted-by":"publisher","award":["1K08DC019957"],"award-info":[{"award-number":["1K08DC019957"]}],"id":[{"id":"10.13039\/100000055","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Laryngoscope Investig Oto"],"published-print":{"date-parts":[[2024,6]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>Cisplatin is known to cause inner ear dysfunction. There is growing evidence that cisplatin\u2010induced demyelination of spiral or Scarpa's ganglion neurons may play an additional role in drug\u2010induced ototoxicity alongside afferent neuron injury. As Schwann cells produce myelin, there may be an opportunity to reduce ototoxic inner ear damage by promoting Schwann cell viability. This work describes a cellular model of cisplatin\u2010induced Schwann cell injury and investigates the ability of the antioxidant N\u2010acetylcysteine to promote Schwann cell viability. A local delivery system of drug\u2010eluting microparticles was then fabricated, characterized, and investigated for bioactivity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      RSC96 rat Schwann cells were dosed with varying concentrations of cisplatin to obtain a dose curve and identify the lethal concentration of 50% of the cells (LC\n                      <jats:sub>50<\/jats:sub>\n                      ). In subsequent experiments, RSC96 cells were co\u2010treated with cisplatin and both resuspended or eluted N\u2010acetylcysteine. Cell viability was assessed with the CCK8 assay.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      The LC\n                      <jats:sub>50<\/jats:sub>\n                      dose of cisplatin was determined to be 3.76\u2009\u03bcM (\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20092.2\u2009x\u200910\n                      <jats:sup>\u221216<\/jats:sup>\n                      ). When co\u2010dosed with cisplatin and a therapeutic concentration of resuspended or eluted N\u2010acetylcysteine, Schwann cells had an increased viability compared to cells dosed with cisplatin alone.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>RSC96 Schwann cell injury following cisplatin insult is characterized in this in vitro model. Cisplatin caused injury at physiologic concentrations and N\u2010acetylcysteine improved cell viability and mitigated this injury. N\u2010acetylcysteine was packaged into microparticles and eluted N\u2010acetylcysteine retained its ability to increase cell viability, thus demonstrating promise as a therapeutic to offset cisplatin\u2010induced ototoxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Level of Evidence<\/jats:title>\n                    <jats:p>N\/A Laryngoscope, 2023.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/lio2.1256","type":"journal-article","created":{"date-parts":[[2024,5,17]],"date-time":"2024-05-17T06:09:32Z","timestamp":1715926172000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["N\u2010acetylcysteine microparticles reduce cisplatin\u2010induced\n                    <scp>RSC96<\/scp>\n                    Schwann cell toxicity"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0009-0009-3088-7283","authenticated-orcid":false,"given":"Katherine","family":"Kedeshian","sequence":"first","affiliation":[{"name":"Department of Head and Neck Surgery David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1897-8635","authenticated-orcid":false,"given":"Michelle","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Larry","family":"Hoffman","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"},{"name":"Vestibular Neuroscience Laboratory, Brain Research Institute David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2759-8271","authenticated-orcid":false,"given":"Ashley","family":"Kita","sequence":"additional","affiliation":[{"name":"Department of Head and Neck Surgery David Geffen School of Medicine at University of California Los Angeles  Los Angeles California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2024,5,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.3390\/toxics3030268"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.toxlet.2015.06.012"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1620\/tjem.219.177"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2005.08.068"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1097\/00001756\u2010200101220\u201000035"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms14487"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.1008499"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0082449"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.3389\/fnmol.2020.608442"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1801109"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1124\/jpet.105.087601"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1155\/2021\/9949453"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.3390\/antiox10060967"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1097\/MAO.0000000000003839"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1002\/bit.26443"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365\u20102125.2004.02082.x"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/000348940111000204"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1089\/ten.2006.0440"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/elsc.202100040"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/polym3031377"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jbm.b.30906"}],"container-title":["Laryngoscope Investigative Otolaryngology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/lio2.1256","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,6,24]],"date-time":"2024-06-24T06:41:07Z","timestamp":1719211267000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/lio2.1256"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,17]]},"references-count":21,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2024,6]]}},"alternative-id":["10.1002\/lio2.1256"],"URL":"https:\/\/doi.org\/10.1002\/lio2.1256","archive":["Portico"],"relation":{"has-preprint":[{"id-type":"doi","id":"10.1101\/2023.10.31.564430","asserted-by":"object"}]},"ISSN":["2378-8038","2378-8038"],"issn-type":[{"value":"2378-8038","type":"print"},{"value":"2378-8038","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,17]]},"assertion":[{"value":"2023-06-23","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication 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