Heart malformation is an early response to valproic acid in developing zebrafish

Rajesh, Venugopalan; Deepan, Natarajan; Vijayakumar, Anitha; Kalaiselvan, Duraisamy; Jayaseelan, Subramanian; Sivakumar, Palanivel; Ganesan, Vellaiyachamy

doi:10.1007/s00210-020-01949-4

Cited by 5 publications

(6 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Series of morphological observations conducted at 120 hpf on the survived larvae of concentrations 0–320 μM instigated that VPA produced teratogenicity effects at concentrations of 160 and 320 μM, through the alterations of total body length, angle of body curvature, area of swim bladder, and pericardial enlargement. The demonstrated results were consistent with the study by Rajesh et al (2020). The failure of the water permeability barrier and increased vascular permeability led to the presence of pericardial edema following VPA exposure (Hill et al, 2004).…”

Section: Discussionsupporting

confidence: 93%

“…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%

“…This study evidently decreased percentage of hatching rate on 160 μM and above treated larvae in comparison to control. In agreement, Rajesh et al (2020) reported that hatching is highly associated with hatching gland enzyme and any alterations on the enzyme can affect the process.…”

Section: Discussionsupporting

confidence: 74%

See 2 more Smart Citations

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

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 91%

See 1 more Smart Citation

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

View full text Add to dashboard Cite

show abstract

“…Some of the tested drugs, such as topiramate and valproic acid, are known to have potential teratogenic and toxic effects [ 74 , 75 , 76 ], so the exposure time to these compounds should be limited. Different publications using the abovementioned compounds show different concentrations and incubation times [ 4 , 28 , 63 , 77 , 78 ].…”

Section: Methodsmentioning

confidence: 99%

A Zebrafish-Based Platform for High-Throughput Epilepsy Modeling and Drug Screening in F0

Locubiche,

Ordóñez,

Abad

et al. 2024

IJMS

View full text Add to dashboard Cite

The zebrafish model has emerged as a reference tool for phenotypic drug screening. An increasing number of molecules have been brought from bench to bedside thanks to zebrafish-based assays over the last decade. The high homology between the zebrafish and the human genomes facilitates the generation of zebrafish lines carrying loss-of-function mutations in disease-relevant genes; nonetheless, even using this alternative model, the establishment of isogenic mutant lines requires a long generation time and an elevated number of animals. In this study, we developed a zebrafish-based high-throughput platform for the generation of F0 knock-out (KO) models and the screening of neuroactive compounds. We show that the simultaneous inactivation of a reporter gene (tyrosinase) and a second gene of interest allows the phenotypic selection of F0 somatic mutants (crispants) carrying the highest rates of mutations in both loci. As a proof of principle, we targeted genes associated with neurodevelopmental disorders and we efficiently generated de facto F0 mutants in seven genes involved in childhood epilepsy. We employed a high-throughput multiparametric behavioral analysis to characterize the response of these KO models to an epileptogenic stimulus, making it possible to employ kinematic parameters to identify seizure-like events. The combination of these co-injection, screening and phenotyping methods allowed us to generate crispants recapitulating epilepsy features and to test the efficacy of compounds already during the first days post fertilization. Since the strategy can be applied to a wide range of indications, this study paves the ground for high-throughput drug discovery and promotes the use of zebrafish in personalized medicine and neurotoxicity assessment.

show abstract

“…It was seen that embryos presented to VPA at 2.5 h postfertilization prompted cardiovascular irregularities like bradycardia, heart abnormality, pericardial sac expansion, and circulatory failure. Embryos which are presented to 100 µM VPA prompted heart mutations, yet there was no impact of heart distortion (Rajesh et al, 2020).…”

Section: Role Of Hdacs/kdacs In Cardiogenesismentioning

confidence: 99%

The role of histone deacetylases in embryonic development

Dsilva

Pai

Shetty

et al. 2022

Molecular Reproduction Devel

View full text Add to dashboard Cite

The basic units of chromatin are nucleosomes, that are made up of DNA wrapped around histone cores. Histone lysine residue is a common location for posttranslational modifications, with acetylation being the second most prevalent. Histone acetyltransferases (HATs/KATs) and histone deacetylases (HDACs/KDACs) regulate histone acetylation, which is important in gene expression control. HDACs/KDACs regulate gene expressions through the repression of the transcription machinery. HDAC/KDAC isoforms play a major role during various stages of embryo development and neurogenesis. In specific, class I and II HDACs/KDACs are involved in cardiac muscle differentiation and development. An insight into different pathways and genes associated with embryonic development, the effect of HDAC/KDAC activity during the embryonic stem cell differentiation, preimplantation, embryo development, gastrulation, and the role of different HDAC/KDAC inhibitors during the process of embryogenesis is summarized in the present review article.

show abstract

Heart malformation is an early response to valproic acid in developing zebrafish

Cited by 5 publications

References 44 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

A Zebrafish-Based Platform for High-Throughput Epilepsy Modeling and Drug Screening in F0

The role of histone deacetylases in embryonic development

Contact Info

Product

Resources

About