{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T23:25:47Z","timestamp":1780615547607,"version":"3.54.1"},"reference-count":46,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2019,12,15]],"date-time":"2019-12-15T00:00:00Z","timestamp":1576368000000},"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":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2020,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:label\/><jats:p>Hair cell (HC) degeneration causes hearing loss in millions of people worldwide. Aminoglycoside exposure is one major cause of sensory HC damage. Aminoglycosides generate free radicals within the inner ear, permanently damaging sensory cells, and thus causing hearing loss. Hearing protection requires strategies to overcome the apparently irreversible loss of HCs in mammals. The nuclear factor of activated T cells (NFAT) inhibitor 11R\u2010VIVIT reportedly protects HCs from gentamicin toxicity. Here we investigated whether the combination of 11R\u2010VIVIT with the antioxidant L\u2010carnitine or N\u2010acetylcysteine could protect mouse cochlear HCs from gentamicin damage. Compared to single\u2010component treatment, combined treatment with 11R\u2010VIVIT plus L\u2010carnitine yielded significant protection from gentamicin, and 11R\u2010VIVIT plus N\u2010acetylcysteine provided almost complete protection of HCs from gentamicin. Caspase activity in organ of Corti was significantly reduced by combined treatment with 11R\u2010VIVIT\u00a0+\u00a0N\u2010acetylcysteine\u00a0+\u00a0gentamicin, compared to 11R\u2010VIVIT\u00a0+\u00a0gentamicin or gentamicin alone. Analysis of relative gene expression by qPCR revealed down\u2010regulation of the pro\u2010apoptotic genes <jats:italic>Fasl<\/jats:italic> and <jats:italic>Casp9<\/jats:italic>, and up\u2010regulation of the antioxidant genes <jats:italic>Hmox1<\/jats:italic> and <jats:italic>Nrf2<\/jats:italic> after treatment with 11R\u2010VIVIT\u00a0+\u00a0N\u2010acetylcysteine\u00a0+\u00a0gentamicin, compared to single\u2010compound treatment or gentamicin alone in cultures. Selective NFAT inhibition by 11R\u2010VIVIT may be a good strategy for preventing gentamicin\u2010induced HC damage. L\u2010carnitine and N\u2010acetylcysteine, with their ROS\u2010reducing properties, contribute to the synergistic effectiveness with 11R\u2010VIVIT by decreasing ROS\u2010induced NFAT translocation. Our data suggest that a combined approach of NFAT inhibition together with an antioxidant, like N\u2010acetylcysteine, could be useful for hearing loss treatment and\/or prevention.<\/jats:p><\/jats:sec><jats:sec><jats:label\/><jats:p>\n<jats:boxed-text content-type=\"graphic\" position=\"anchor\"><jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/jnc14921-fig-0007-m.png\"><jats:alt-text>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>\n<\/jats:p><jats:p>Cover Image for this issue: <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"https:\/\/doi.org\/10.1111\/jnc.14759\">https:\/\/doi.org\/10.1111\/jnc.14759<\/jats:ext-link>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.14921","type":"journal-article","created":{"date-parts":[[2019,11,22]],"date-time":"2019-11-22T13:26:03Z","timestamp":1574429163000},"page":"519-529","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Combination of antioxidants and NFAT (nuclear factor of activated T cells) inhibitor protects auditory hair cells from ototoxic insult"],"prefix":"10.1111","volume":"154","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3761-7253","authenticated-orcid":false,"given":"Marijana","family":"Sekulic\u2010Jablanovic","sequence":"first","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Krystsina","family":"Voronkova","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Bodmer","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"},{"name":"Clinic for Otolaryngology, Head and Neck Surgery University Hospital Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0741-9774","authenticated-orcid":false,"given":"Vesna","family":"Petkovic","sequence":"additional","affiliation":[{"name":"Department of Biomedicine University of Basel Basel Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2019,12,15]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/10715762.2018.1468564"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1567-5769(01)00105-9"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1080\/00016480601110188"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1159\/000071996"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2017.457"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/jnc.13880"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2008.02.005"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0378-5955(96)00075-5"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.4103\/1463-1741.64972"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.freeradbiomed.2015.04.021"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.heares.2017.12.004"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcf.2017.01.006"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hipo.20934"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.4103\/1673-5374.224371"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1155\/2011\/937861"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.3389\/fncel.2017.00308"},{"key":"e_1_2_7_18_1","first-page":"645","article-title":"Fas mediates apoptosis and oxidant\u2010induced cell death in cultured hRPE cells","volume":"41","author":"Jiang","year":"2000","journal-title":"Investigative Ophthalmology & Visual Science"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508053102"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/0091-7435(86)90005-8"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.1177\/0194599816639297"},{"key":"e_1_2_7_22_1","first-page":"2611","article-title":"Preventing amikacin related ototoxicity with N\u2010acetylcysteine in patients undergoing peritoneal dialysis","volume":"272","author":"Kocyigit I.","year":"2015","journal-title":"European archives of oto\u2010rhino\u2010laryngology: Official journal of the European Federation of Oto\u2010Rhino\u2010Laryngological Societies (EUFOS): Affiliated with the German Society for Oto\u2010Rhino\u2010Laryngology. 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