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Article

Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model

by
Eunhye Lee
1,
Amit Banik
2,
Ki-Baek Lee
3,
Seung Min Sim
1,
Ah Hyun Kil
4,
Byung Joon Hwang
4,5,* and
Yun Kee
4,6,*
1
Department of Biomedical Science, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea
2
Interdisciplinary Graduate Program in Environmental and Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea
3
Zefit Inc., Daegu 43017, Republic of Korea
4
Department of Molecular Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea
5
Department of Molecular Bioscience, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea
6
Division of Biomedical Convergence, College of Biomedical Science, Kangwon National University, Chuncheon 24341, Republic of Korea
*
Authors to whom correspondence should be addressed.
Molecules 2024, 29(11), 2572; https://doi.org/10.3390/molecules29112572
Submission received: 10 April 2024 / Revised: 20 May 2024 / Accepted: 28 May 2024 / Published: 30 May 2024
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Abstract

Epilepsy is a prevalent neurological disorder characterized by recurrent seizures. 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 µM within the effective range. The median lethal dose of VA in adult zebrafish was > 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.
Keywords: validamycin A; antibiotic fungicide; anti-seizure activity; zebrafish epilepsy model; electroencephalogram; angular velocity validamycin A; antibiotic fungicide; anti-seizure activity; zebrafish epilepsy model; electroencephalogram; angular velocity
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MDPI and ACS Style

Lee, E.; Banik, A.; Lee, K.-B.; Sim, S.M.; Kil, A.H.; Hwang, B.J.; Kee, Y. Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model. Molecules 2024, 29, 2572. https://doi.org/10.3390/molecules29112572

AMA Style

Lee E, Banik A, Lee K-B, Sim SM, Kil AH, Hwang BJ, Kee Y. Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model. Molecules. 2024; 29(11):2572. https://doi.org/10.3390/molecules29112572

Chicago/Turabian Style

Lee, Eunhye, Amit Banik, Ki-Baek Lee, Seung Min Sim, Ah Hyun Kil, Byung Joon Hwang, and Yun Kee. 2024. "Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model" Molecules 29, no. 11: 2572. https://doi.org/10.3390/molecules29112572

APA Style

Lee, E., Banik, A., Lee, K.-B., Sim, S. M., Kil, A. H., Hwang, B. J., & Kee, Y. (2024). Assessment of the Novel Anti-Seizure Potential of Validamycin A Using Zebrafish Epilepsy Model. Molecules, 29(11), 2572. https://doi.org/10.3390/molecules29112572

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