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Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder

Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20...

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Main Authors: Saleh Hodin, Nur Atikah, Chong, Siok Geok, Abu Bakar, Noraini, Mohd Fahmi, Muhammad Syafiq Akmal, Ramlan, Nurul Farhana, Zulkifli Hamid, Nik Nur Aini Zulaikha, Mohd Fadzar, Muhammad Syuqor Iqbal, Zulkifli, Abdul Rahman, Norazhar, Anis Irfan, Mastuki, Siti Nurulhuda, Mohd Faudzi, Siti Munirah, Wan Ibrahim, Wan Norhamidah, Azmai, Mohammad Noor Amal
Format: Article
Published: John Wiley 2023
Online Access:http://psasir.upm.edu.my/id/eprint/108327/
https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2227
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spelling my.upm.eprints.1083272025-03-04T03:25:19Z http://psasir.upm.edu.my/id/eprint/108327/ Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder Saleh Hodin, Nur Atikah Chong, Siok Geok Abu Bakar, Noraini Mohd Fahmi, Muhammad Syafiq Akmal Ramlan, Nurul Farhana Zulkifli Hamid, Nik Nur Aini Zulaikha Mohd Fadzar, Muhammad Syuqor Iqbal Zulkifli, Abdul Rahman Norazhar, Anis Irfan Mastuki, Siti Nurulhuda Mohd Faudzi, Siti Munirah Wan Ibrahim, Wan Norhamidah Azmai, Mohammad Noor Amal Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤.05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥.005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels. John Wiley 2023 Article PeerReviewed Saleh Hodin, Nur Atikah and Chong, Siok Geok and Abu Bakar, Noraini and Mohd Fahmi, Muhammad Syafiq Akmal and Ramlan, Nurul Farhana and Zulkifli Hamid, Nik Nur Aini Zulaikha and Mohd Fadzar, Muhammad Syuqor Iqbal and Zulkifli, Abdul Rahman and Norazhar, Anis Irfan and Mastuki, Siti Nurulhuda and Mohd Faudzi, Siti Munirah and Wan Ibrahim, Wan Norhamidah and Azmai, Mohammad Noor Amal (2023) Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder. Birth Defects Research, 115 (16). pp. 1475-1485. ISSN 2472-1727; eISSN: 2472-1727 https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2227 10.1002/bdr2.2227
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
description Valproic acid (VPA) is a widely prescribed antiepileptic drug with various medicinal efficacies. Accumulated evidence implied that prenatal exposure to VPA is highly associated with autism spectrum disorder (ASD). In this study, the zebrafish were exposed to a set of VPA concentrations (0, 5, 10, 20, 40, 80, 160, 320, 640, 1280, and 2560 μM) at 5 h post fertilization (hpf) to 120 hpf. The adverse effects of VPA were extensively studied through the evaluations on the mortality, heartbeats, spontaneous tail coiling, and hatching rate. Morphological observations were conducted at 120 hpf, following the exposure termination. Basic locomotor responses and anxiety-like behavioral alterations evaluated for behavioral impairments are the hallmark feature of ASD. The exposure to VPA at teratogenic concentrations reduced the aforementioned parameters in a dose-dependent manner (p ≤.05). At the selected non-teratogenic concentrations of VPA, the treated larvae demonstrated profound alterations of basic locomotor responses. No significant changes of anxiety and thigmotactic behaviors were observed on the VPA-treated fish compared to the control (p ≥.005). This study depicted that embryonic zebrafish exposure to VPA produced significant toxicity and teratogenicity effects as well as the alterations of basic behavioral responses. Overall, this study provides a fundamental insight of the toxicity effects at morphological and behavioral levels to facilitate the understanding of ASD mechanisms at different molecular levels.
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author Saleh Hodin, Nur Atikah
Chong, Siok Geok
Abu Bakar, Noraini
Mohd Fahmi, Muhammad Syafiq Akmal
Ramlan, Nurul Farhana
Zulkifli Hamid, Nik Nur Aini Zulaikha
Mohd Fadzar, Muhammad Syuqor Iqbal
Zulkifli, Abdul Rahman
Norazhar, Anis Irfan
Mastuki, Siti Nurulhuda
Mohd Faudzi, Siti Munirah
Wan Ibrahim, Wan Norhamidah
Azmai, Mohammad Noor Amal
spellingShingle Saleh Hodin, Nur Atikah
Chong, Siok Geok
Abu Bakar, Noraini
Mohd Fahmi, Muhammad Syafiq Akmal
Ramlan, Nurul Farhana
Zulkifli Hamid, Nik Nur Aini Zulaikha
Mohd Fadzar, Muhammad Syuqor Iqbal
Zulkifli, Abdul Rahman
Norazhar, Anis Irfan
Mastuki, Siti Nurulhuda
Mohd Faudzi, Siti Munirah
Wan Ibrahim, Wan Norhamidah
Azmai, Mohammad Noor Amal
Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
author_facet Saleh Hodin, Nur Atikah
Chong, Siok Geok
Abu Bakar, Noraini
Mohd Fahmi, Muhammad Syafiq Akmal
Ramlan, Nurul Farhana
Zulkifli Hamid, Nik Nur Aini Zulaikha
Mohd Fadzar, Muhammad Syuqor Iqbal
Zulkifli, Abdul Rahman
Norazhar, Anis Irfan
Mastuki, Siti Nurulhuda
Mohd Faudzi, Siti Munirah
Wan Ibrahim, Wan Norhamidah
Azmai, Mohammad Noor Amal
author_sort Saleh Hodin, Nur Atikah
title Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
title_short Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
title_full Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
title_fullStr Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
title_full_unstemmed Toxicity and teratogenicity effects of valproic acid on zebrafish (Danio rerio) embryos in relation to autism spectrum disorder
title_sort toxicity and teratogenicity effects of valproic acid on zebrafish (danio rerio) embryos in relation to autism spectrum disorder
publisher John Wiley
publishDate 2023
url http://psasir.upm.edu.my/id/eprint/108327/
https://onlinelibrary.wiley.com/doi/10.1002/bdr2.2227
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score 13.244413

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