{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T19:53:43Z","timestamp":1789588423505,"version":"build-2803163510"},"reference-count":40,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,21]],"date-time":"2021-12-21T00:00:00Z","timestamp":1640044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2018M3C1B7021997"],"award-info":[{"award-number":["NRF-2018M3C1B7021997"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["2021R1A2C101417611"],"award-info":[{"award-number":["2021R1A2C101417611"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Korea Medical Device Development Fund grant","award":["Project Number: 202013C05"],"award-info":[{"award-number":["Project Number: 202013C05"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>High-dose salicylate induces temporary moderate hearing loss and the perception of a high-pitched tinnitus in humans and animals. Previous studies demonstrated that high doses of salicylate increase N-methyl-d-aspartate (NMDA) receptor levels, resulting in a rise in Ca2+ influx and induction of excitotoxicity. Glutamate excitotoxicity is associated with failure in the maintenance of calcium homeostasis, mitochondrial dysfunction, and production of reactive oxygen species (ROS). Valproic acid (VPA) is widely used for the management of bipolar disorder, epilepsy, and migraine headaches, and is known to regulate NMDA receptor activity. In this study, we examined the beneficial effects of VPA in a salicylate-induced tinnitus model in vitro and in vivo. Cells were pretreated with VPA followed by salicylate treatment. The expression levels of NMDA receptor subunit NR2B, phosphorylated cAMP response element-binding protein\u2014an apoptosis marker, and intracellular levels of ROS were measured using several biochemical techniques. We observed increased expression of NR2B and its related genes TNF\u03b1 and ARC, increased intracellular ROS levels, and induced expression of cleaved caspase-3. These salicylate-induced changes were attenuated in the neuronal cell line SH-SY5Y and rat cortical neurons after VPA pretreatment. Together, these results provide evidence of the beneficial effects of VPA in a salicylate-induced temporary hearing loss and tinnitus model.<\/jats:p>","DOI":"10.3390\/ijms23010023","type":"journal-article","created":{"date-parts":[[2021,12,22]],"date-time":"2021-12-22T01:08:09Z","timestamp":1640135289000},"page":"23","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Neuroprotective Effect of Valproic Acid on Salicylate-Induced Tinnitus"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3527-8216","authenticated-orcid":false,"given":"Anji","family":"Song","sequence":"first","affiliation":[{"name":"Department of Biology, College of Natural Science, Chosun University, Gwangju 61452, Korea"},{"name":"BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2149-5095","authenticated-orcid":false,"given":"Gwang-Won","family":"Cho","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Science, Chosun University, Gwangju 61452, Korea"},{"name":"BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2223-8549","authenticated-orcid":false,"given":"Karthikeyan A.","family":"Vijayakumar","sequence":"additional","affiliation":[{"name":"Department of Biology, College of Natural Science, Chosun University, Gwangju 61452, Korea"},{"name":"BK21 FOUR Education Research Group for Age-Associated Disorder Control Technology, Department of Integrative Biological Science, Chosun University, Gwangju 61452, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2451-0374","authenticated-orcid":false,"given":"Changjong","family":"Moon","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0998-3069","authenticated-orcid":false,"given":"Mary Jasmin","family":"Ang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Anatomy, College of Veterinary Medicine and BK21 FOUR Program, Chonnam National University, Gwangju 61186, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jahae","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Nuclear Medicine, Chonnam National University Hospital, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1613-4209","authenticated-orcid":false,"given":"Ilyong","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Biomedical Engineering, School of Medicine, Dankook University, Cheonan 31116, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4084-2301","authenticated-orcid":false,"given":"Chul Ho","family":"Jang","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology, Chonnam National University Medical School, Gwangju 61469, Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.3109\/14992027.2010.551220","article-title":"Tinnitus and its risk factors in the Beaver Dam offspring study","volume":"50","author":"Nondahl","year":"2011","journal-title":"Int. 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