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Validamycin A (VA) is an antibiotic fungicide that inhibits trehalase activity and is widely used for crop protection in agriculture. In this study, we identified a novel function of VA as a potential anti-seizure medication in a zebrafish epilepsy model. Electroencephalogram (EEG) analysis demonstrated that VA reduced pentylenetetrazol (PTZ)-induced seizures in the brains of larval and adult zebrafish. Moreover, VA reduced PTZ-induced irregular movement in a behavioral assessment of adult zebrafish. The developmental toxicity test showed no observable anatomical alteration when the zebrafish larvae were treated with VA up to 10 \u00b5M within the effective range. The median lethal dose of VA in adult zebrafish was &gt; 14,000 mg\/kg. These results imply that VA does not demonstrate observable toxicity in zebrafish at concentrations effective for generating anti-seizure activity in the EEG and alleviating abnormal behavior in the PTZ-induced epileptic model. Furthermore, the effectiveness of VA was comparable to that of valproic acid. These results indicate that VA may have a potentially safer anti-seizure profile than valproic acid, thus offering promising prospects for its application in agriculture and medicine.<\/jats:p>","DOI":"10.3390\/molecules29112572","type":"journal-article","created":{"date-parts":[[2024,5,30]],"date-time":"2024-05-30T06:08:14Z","timestamp":1717049294000},"page":"2572","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model"],"prefix":"10.3390","volume":"29","author":[{"given":"Eunhye","family":"Lee","sequence":"first","affiliation":[{"name":"Department of Biomedical Science, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3795-9383","authenticated-orcid":false,"given":"Amit","family":"Banik","sequence":"additional","affiliation":[{"name":"Interdisciplinary Graduate Program in Environmental and Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ki-Baek","family":"Lee","sequence":"additional","affiliation":[{"name":"Zefit Inc., Daegu 43017, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seung Min","family":"Sim","sequence":"additional","affiliation":[{"name":"Department of Biomedical Science, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ah Hyun","family":"Kil","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung Joon","family":"Hwang","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"},{"name":"Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2764-1468","authenticated-orcid":false,"given":"Yun","family":"Kee","sequence":"additional","affiliation":[{"name":"Department of Molecular Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"},{"name":"Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,5,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1094\/MPMI-08-20-0211-R","article-title":"Validamycin A induces broad-spectrum resistance involving salicylic acid and jasmonic acid\/ethylene signaling pathways","volume":"33","author":"Bian","year":"2020","journal-title":"Mol. Plant Microbe Interact."},{"key":"ref_2","first-page":"217","article-title":"Analysis of validamycin as a potential antifungal compound against Candida albicans","volume":"16","author":"Valentin","year":"2013","journal-title":"Int. Microbiol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"Plabutong, N., Ekronarongchai, S., Niwetbowornchai, N., Edwards, S.W., Virakul, S., Chiewchengchol, D., and Thammahong, A. (2020). The inhibitory effect of validamycin A on aspergillus flavus. Int. J. Microbiol., 2020.","DOI":"10.1155\/2020\/3972415"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1417","DOI":"10.7164\/antibiotics.44.1417","article-title":"All eight possible mono-beta-D-glucosides of validoxylamine A. II. Biological activities","volume":"44","author":"Asano","year":"1991","journal-title":"Jpn. J. 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Res."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.yebeh.2016.11.012","article-title":"Cannabinoids in treatment-resistant epilepsy: A review","volume":"70","author":"Gloss","year":"2017","journal-title":"Epilepsy Behav."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.neubiorev.2020.06.010","article-title":"Seizing the moment: Zebrafish epilepsy models","volume":"116","author":"Gawel","year":"2020","journal-title":"Neurosci. Biobehav. Rev."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1080\/01677063.2018.1445247","article-title":"High-throughput behavioral assay to investigate seizure sensitivity in zebrafish implicates ZFHX3 in epilepsy","volume":"32","author":"Fuller","year":"2018","journal-title":"J. Neurogenet."},{"key":"ref_10","doi-asserted-by":"crossref","unstructured":"Cho, S.J., Park, E., Baker, A., and Reid, A.Y. (2020). Age Bias in Zebrafish Models of Epilepsy: What can we learn from old fish?. Front. Cell Dev. Biol., 8.","DOI":"10.3389\/fcell.2020.573303"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"S133","DOI":"10.1002\/epi4.12581","article-title":"Antiseizure medication discovery: Recent and future paradigm shifts","volume":"7","author":"Talevi","year":"2022","journal-title":"Epilepsia Open"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"935","DOI":"10.1007\/s40263-021-00827-8","article-title":"The pharmacology and clinical efficacy of antiseizure medications: From bromide salts to cenobamate and beyond","volume":"35","author":"Loscher","year":"2021","journal-title":"CNS Drugs"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Lee, Y., Lee, K.J., Jang, J.W., Lee, S.I., and Kim, S. (2020). An EEG system to detect brain signals from multiple adult zebrafish. Biosens. Bioelectron., 164.","DOI":"10.1016\/j.bios.2020.112315"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1089\/zeb.2020.1874","article-title":"Noninvasive Multielectrode array for brain and spinal cord local field potential recordings from live zebrafish larvae","volume":"17","author":"Tomasello","year":"2020","journal-title":"Zebrafish"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1055424","DOI":"10.3389\/fphar.2022.1055424","article-title":"Zebrafish EEG predicts the efficacy of antiepileptic drugs","volume":"13","author":"Shin","year":"2022","journal-title":"Front. Pharmacol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"226","DOI":"10.5694\/mja17.00951","article-title":"The management of epilepsy in children and adults","volume":"208","author":"Perucca","year":"2018","journal-title":"Med. J. Aust."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1016\/j.chemosphere.2019.04.061","article-title":"3D light-sheet assay assessing novel valproate-associated cardiotoxicity and folic acid relief in zebrafish embryogenesis","volume":"227","author":"Ki","year":"2019","journal-title":"Chemosphere"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Banik, A., Eum, J., Hwang, B.J., and Kee, Y. (2023). Differential neuroprotective effects of N-acetylcysteine against dithianon toxicity in glutamatergic, dopaminergic, and GABAergic neurons: Assessment using zebrafish. 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