3D light-sheet assay assessing novel valproate-associated cardiotoxicity and folic acid relief in zebrafish embryogenesis

Ki, Seoyoung; Kwon, Seung‐Hae; Eum, Juneyong; Raslan, Ahmed A.; Kim, Kil-Nam; Hwang, Byung Joon; Kee, Yun

doi:10.1016/j.chemosphere.2019.04.061

Cited by 12 publications

(7 citation statements)

References 78 publications

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“…Reduced number of heartbeats became significantly visible compared to control. The result obtained interestingly coincide with other studies whereas exposure to VPA decreased the number of heartbeats especially at 100 μM (Ki et al, 2019; Rajesh et al, 2020). This might be due to the alteration of myl7 gene expression during early cardiac development that will progress to an abnormal heart looping and chamber formation (Ki et al, 2019).…”

Section: Discussionsupporting

confidence: 91%

“…The result obtained interestingly coincide with other studies whereas exposure to VPA decreased the number of heartbeats especially at 100 μM (Ki et al, 2019; Rajesh et al, 2020). This might be due to the alteration of myl7 gene expression during early cardiac development that will progress to an abnormal heart looping and chamber formation (Ki et al, 2019). Hatching is a critical process of zebrafish regulated by the biochemical and physical mechanisms through the secretion of choriolysin (Capriello et al, 2019).…”

Section: Discussionsupporting

confidence: 91%

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

Saleh Hodin,

Chong,

Bakar

et al. 2023

Birth Defects Research

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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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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 91%

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

Saleh Hodin,

Chong,

Bakar

et al. 2023

Birth Defects Research

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“…VPA was reported to decrease methylation levels in the promoters of specific genes (tumor suppressors), but increase overall methylation, which can be attributed to its anticancer properties [118]. VPA is used in the form of concentrated drops to fortify some diets including the ketogenic diet [119]. Therefore, if the epigenetic diet is a promising avenue for migraine treatment, studies on diets fortified with VPA should be undertaken.…”

Section: Discussionmentioning

confidence: 99%

Is an “Epigenetic Diet” for Migraines Justified? The Case of Folate and DNA Methylation

Fila

Chojnacki

et al. 2019

Nutrients

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Migraines are a common disease with limited treatment options and some dietary factors are recognized to trigger headaches. Although migraine pathogenesis is not completely known, aberrant DNA methylation has been reported to be associated with its occurrence. Folate, an essential micronutrient involved in one-carbon metabolism and DNA methylation, was shown to have beneficial effects on migraines. Moreover, the variability of the methylenetetrahydrofolate reductase gene, important in both folate metabolism and migraine pathogenesis, modulates the beneficial effects of folate for migraines. Therefore, migraine could be targeted by a folate-rich, DNA methylation-directed diet, but there are no data showing that beneficial effects of folate consumption result from its epigenetic action. Furthermore, contrary to epigenetic drugs, epigenetic diets contain many compounds, some yet unidentified, with poorly known or completely unknown potential to interfere with the epigenetic action of the main dietary components. The application of epigenetic diets for migraines and other diseases requires its personalization to the epigenetic profile of a patient, which is largely unknown. Results obtained so far do not warrant the recommendation of any epigenetic diet as effective in migraine prevention and therapy. Further studies including a folate-rich diet fortified with valproic acid, another modifier of epigenetic profile effective in migraine prophylaxis, may help to clarify this issue.

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“…Three heart tube morphologies occur in zebrafish: dextral loop (D-loop), leftward loop (L-loop), or unloop. Zebrafish is limited to exploring the phenotypes specific to vertebrates with four chambers; however, its advantage of better survival from cardiac defects through embryonic development allows the exploration of detailed gene function during development and the histopathology of visceral organs over the lifetime (Stainier et al 1996 ; Ki et al 2019 ).…”

Section: Introductionmentioning

confidence: 99%

“…Laterality defects such as cardiac looping appear during zebrafish development, and it is possible to detect abnormal morphology during embryonic development to a certain extent using conventional microscopy as well as advanced imaging technologies including single plane illumination microscopy as previously applied in the lab (Park et al 2015 ; Eum et al 2016 ; Ki et al 2019 ). Here, we examined the combinatorial laterality defects of the parapineal and cardiac looping in early embryos by inducing the laterality defect under experimental pressure and investigated the relationship between the brain and heart in the establishment of left-right asymmetry.…”

Section: Introductionmentioning

confidence: 99%

Histopathological assessment of laterality defects in zebrafish development

Chowdhury

Raslan

Lee

et al. 2021

Animal Cells and Systems

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Laterality defects during embryonic development underlie the aetiology of various clinical symptoms of neuropathological and cardiovascular disorders; however, experimental approaches to understand the underlying mechanisms are limited due to the complex organ systems of vertebrate models. Zebrafish have the ability to survive even when the heart stops beating for a while during early embryonic development and those adults with cardiac abnormalities. Therefore, we induced laterality defects and investigated the occurrence of situs solitus, situs inversus, and situs ambiguus in zebrafish development. Histopathological analysis revealed heterotaxy in both embryos and juvenile fish. Additionally, randomization of left-right asymmetry of the brain and heart in individual zebrafish embryos under artificial experimental pressure further demonstrated the advantage of transparent zebrafish embryos as an experimental tool to select or reduce the embryos with laterality defects during early embryonic development for long-term studies, including behavioural and cognitive neuroscience investigations.

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3D light-sheet assay assessing novel valproate-associated cardiotoxicity and folic acid relief in zebrafish embryogenesis

Cited by 12 publications

References 78 publications

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

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

Is an “Epigenetic Diet” for Migraines Justified? The Case of Folate and DNA Methylation

Histopathological assessment of laterality defects in zebrafish development

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