Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model
Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epilepti...
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MDPI AG
2021-01-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/3/1285 |
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| author | Seong Soon Kim Hyemin Kan Kyu-Seok Hwang Jung Yoon Yang Yuji Son Dae-Seop Shin Byung Hoi Lee Se Hwan Ahn Jin Hee Ahn Sung-Hee Cho Myung Ae Bae |
| author_facet | Seong Soon Kim Hyemin Kan Kyu-Seok Hwang Jung Yoon Yang Yuji Son Dae-Seop Shin Byung Hoi Lee Se Hwan Ahn Jin Hee Ahn Sung-Hee Cho Myung Ae Bae |
| author_sort | Seong Soon Kim |
| collection | DOAJ |
| description | Epilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents. |
| first_indexed | 2024-03-09T03:26:12Z |
| format | Article |
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| language | English |
| last_indexed | 2024-03-09T03:26:12Z |
| publishDate | 2021-01-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-31515a871b8c4967b6182604aee17c1f2023-12-03T15:02:32ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-01-01223128510.3390/ijms22031285Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish ModelSeong Soon Kim0Hyemin Kan1Kyu-Seok Hwang2Jung Yoon Yang3Yuji Son4Dae-Seop Shin5Byung Hoi Lee6Se Hwan Ahn7Jin Hee Ahn8Sung-Hee Cho9Myung Ae Bae10Bio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaDepartment of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaDepartment of Chemistry, Gwangju Institute of Science and Technology, Gwangju 61005, KoreaChemical Analysis Center, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaBio & Drug Discovery Division, Korea Research Institute of Chemical Technology, Daejeon 34114, KoreaEpilepsy is one of the most common neurological disorders, and it is characterized by spontaneous seizures. In a previous study, we identified 4-(2-chloro-4-fluorobenzyl)-3-(2-thienyl)-1,2,4-oxadiazol-5(4H)-one (GM-90432) as a novel anti-epileptic agent in chemically- or genetically-induced epileptic zebrafish and mouse models. In this study, we investigated the anti-epileptic effects of GM-90432 through neurochemical profiling-based approach to understand the neuroprotective mechanism in a pentylenetetrazole (PTZ)-induced epileptic seizure zebrafish model. GM-90432 effectively improved PTZ-induced epileptic behaviors via upregulation of 5-hydroxytryptamine, 17-β-estradiol, dihydrotestosterone, progesterone, 5α -dihydroprogesterone, and allopregnanolone levels, and downregulation of normetanephrine, gamma-aminobutyric acid, and cortisol levels in brain tissue. GM-90432 also had a protective effect against PTZ-induced oxidative stress and zebrafish death, suggesting that it exhibits biphasic neuroprotective effects via scavenging of reactive oxygen species and anti-epileptic activities in a zebrafish model. In conclusion, our results suggest that neurochemical profiling study could be used to better understand of anti-epileptic mechanism of GM-90432, potentially leading to new drug discovery and development of anti-seizure agents.https://www.mdpi.com/1422-0067/22/3/1285epilepsyneurotransmitterneurosteroidmetabolic alterationzebrafish |
| spellingShingle | Seong Soon Kim Hyemin Kan Kyu-Seok Hwang Jung Yoon Yang Yuji Son Dae-Seop Shin Byung Hoi Lee Se Hwan Ahn Jin Hee Ahn Sung-Hee Cho Myung Ae Bae Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model International Journal of Molecular Sciences epilepsy neurotransmitter neurosteroid metabolic alteration zebrafish |
| title | Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model |
| title_full | Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model |
| title_fullStr | Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model |
| title_full_unstemmed | Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model |
| title_short | Neurochemical Effects of 4-(2Chloro-4-Fluorobenzyl)-3-(2-Thienyl)-1,2,4-Oxadiazol-5(4H)-One in the Pentylenetetrazole (PTZ)-Induced Epileptic Seizure Zebrafish Model |
| title_sort | neurochemical effects of 4 2chloro 4 fluorobenzyl 3 2 thienyl 1 2 4 oxadiazol 5 4h one in the pentylenetetrazole ptz induced epileptic seizure zebrafish model |
| topic | epilepsy neurotransmitter neurosteroid metabolic alteration zebrafish |
| url | https://www.mdpi.com/1422-0067/22/3/1285 |
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