Psoralen Induces Developmental Toxicity in Zebrafish Embryos/Larvae Through Oxidative Stress, Apoptosis, and Energy Metabolism Disorder

Xia, Qing; Wei, Lingying; Zhang, Yun; Kong, Haotian; Shi, Yanyun; Wang, Xue; Chen, Xiqiang; Han, Liwen; Liu, Kechun

doi:10.3389/fphar.2018.01457

Cited by 54 publications

(51 citation statements)

References 39 publications

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“…Zebrafish (Danio rerio) has been widely accepted as a prominent vertebrate model for toxicological and developmental studies in recent years because of the high fecundity, rapid organogenesis, short generation, and transparent body of embryos and larvae, and so on (Hill et al, 2005;McGrath and Li, 2008;Haque and Ward, 2018;Xia et al, 2018;Al-Samadi et al, 2019;Van Sebille et al, 2019). In addition, it shares high degree of genetic conservation which makes it have additional advantages over traditional animal models (Crawford et al, 2008;Jia et al, 2019).…”

Section: Introductionmentioning

confidence: 99%

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

et al. 2020

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E804, a derivative of indirubin, have multi-biological activities such as anticancer and antiinflammatory activities, but little is known about its developmental toxicity. In this study, we investigated the toxicity of E804 on the developments of zebrafish embryos. Our results showed that E804 treatment caused a significant increase of the malformation rate compared with the control groups. Pericardial edema and curved body shape were the most morphological abnormalities observed in E804-treated group. The hatching rates and body length of the zebrafish larvae was significantly decreased in E804-treated groups. E804 also affect the development of heart, liver, phagocytes and vascular formation. Further studies showed that the level of reactive oxygen species was significantly increased. The activity of total superoxide dismutase decreased and the concentration of malondialdehyde were increased. Much more apoptotic cells were detected in E804-treated group, compared with the control. In addition, geneexpression results showed that the pathways of oxidative stress and apoptosis were provoked in E804 treated groups. Taken together, our findings will be helpful to understanding E804-induced developmental toxicity and the underlying mechanism.

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Section: Introductionmentioning

confidence: 99%

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

et al. 2020

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“…Several morphological abnormalities such as the yolk retention, swim-bladder deficiency, pericardial oedema, and curved body shape were observed at 24 to 96 hpf in psoralen-treated embryos. Also, it was observed that psoralen exerted toxic effects on the developing heart, liver, phagocytes, and nervous system [40]. Increased generation of reactive oxygen species and malondialdehyde concentrations and inhibition of total superoxide dismutase activity in the zebrafish embryo indicate oxidative stress caused by the psoralen [40].…”

Section: Resultsmentioning

confidence: 99%

“…GA at 0.5–1.0 μ M exhibited specific fin developmental defect with the phenotype resembling those caused by thalidomide. The amount of GA absorbed by the zebrafish embryos appeared to be time dependent [40]. It was further revealed GA upregulated ALDH12 (Aldehyde Dehydrogenase 1 Family Member A2) and downregulated CYP26A1 (cytochrome P450 family 26 subfamily A member 1) at 8hpf.…”

Section: Resultsmentioning

confidence: 99%

Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

Jayasinghe

Jayawardena

2019

Evidence-Based Complementary and Alternative Medicine

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Herbal remedies have been practiced by humans over centuries and therefore possess time-proven safety. However, it is imperative to evaluate the toxic effects of herbal medicine to confirm their safety, particularly when developing therapeutic leads. Use of laboratory animals such as rats, mice, and rabbits was considered as gold standard in herbal toxicity assessments. However, in the last few decades, the ethical consideration of using higher vertebrates for toxicity testing has become more contentious. Thus, possible alternative models entailing lower vertebrates such as zebrafish were introduced. The zebrafish embryotoxicity model is at the forefront of toxicology assessment due to the transparent nature of embryos, low cost, short cycle, higher fecundity, and genetic redundancy to the humans. Recently, its application has been extended to herbal toxicology. The present review intends to provide a comprehensive assembly of studies that applied the zebrafish embryo model for the assessment of herbal toxicity. A systematic literature survey was carried out in popular scientific databases. The literature search identified a total of 1014 articles in PubMed = 12, Scopus SciVerse® = 623, and Google Scholar = 1000. After screening, 25 articles were included in this review, and they were categorized into three groups in which the zebrafish embryotoxicity assay has been applied to investigate the toxicity of (1) polyherbal formulae/medical prescription (2 full texts), (2) crude extracts (12 full texts), and (3) phytocompounds/isolated constituents (11 full texts). These studies have investigated the toxicity of 6 polyherbal formulae, 16 crude extracts, and more than 30 phytocompounds/isolated constituents using the zebrafish embryotoxicity model. Moreover, this model has explicated the teratogenic effects and specific organ toxicities such as the kidney, heart, and liver. Furthermore, in some studies, the molecular mechanisms underlying the toxicity of herbal medicine have been elucidated. This comprehensive collection of scientific data solidifies the zebrafish embryo model as an effective model system for studying toxicological effects of a broad spectrum of herbal remedies. Henceforth, it provides a novel insight into the toxicity assessment of herbal medicine.

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“…Furthermore, down-regulated expression levels of ppara1, fas, and hmgcra demonstrated psoralen-induced abnormal lipid metabolism, causing zebrafish embryo/larval developmental toxicity, reducing the rate of hatching in zebrafish, diminishing their body length, and significantly increasing the rate of deformity. Because the yolk is the only source of energy during zebrafish embryo development, yolk retention, pericardial edema, fish sting defects, and flexion were observed in zebrafish larvae, in addition to toxic effects to the developing heart, liver, phagocytes, and nervous system (Xia et al, 2018). The BeWo human placental cell line is derived from choriocarcinoma and is used as a rate-limiting barrier model for drug and nutrient exchange between mother and fetus in the placenta (Hawkins et al, 2018;Zhang et al, 2020).…”

Section: Embryotoxicitymentioning

confidence: 99%

A Review of the Pharmacological Properties of Psoralen

et al. 2020

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Psoralen is the principal bioactive component in the dried fruits of Cullen corylifolium (L.) Medik (syn. Psoralea corylifolia L), termed "Buguzhi" in traditional Chinese medicine (TCM). Recent studies have demonstrated that psoralen displays multiple bioactive properties, beneficial for the treatment of osteoporosis, tumors, viruses, bacteria, and inflammation. The present review focuses on the research evidence relating to the properties of psoralen gathered over recent years. Firstly, multiple studies have demonstrated that psoralen exerts strong anti-osteoporotic effects via regulation of osteoblast/osteoclast/chondrocyte differentiation or activation due to the participation in multiple molecular mechanisms of the wnt/b-catenin, bone morphogenetic protein (BMP), inositol-requiring enzyme 1 (IRE1)/ apoptosis signaling kinase 1 (ASK1)/c-jun N-terminal kinase (JNK) and the Protein Kinase B (AKT)/activator protein-1 (AP-1) axis, and the expression of miR-488, peroxisome proliferators-activated receptor-gamma (PPARg), and matrix metalloproteinases (MMPs). In addition, the antitumor properties of psoralen are associated with the induction of ER stress-related cell death via enhancement of PERK: Pancreatic Endoplasmic Reticulum Kinase (PERK)/activating transcription factor (ATF), 78kD glucose-regulated protein (GRP78)/C/EBP homologous protein (CHOP), and 94kD glucose-regulated protein (GRP94)/CHOP signaling, and inhibition of P-glycoprotein (P-gp) or ATPase that overcomes multidrug resistance. Furthermore, multiple articles have shown that the antibacterial, anti-inflammatory and neuroprotective effects of psoralen are a result of its interaction with viral polymerase (Pol), destroying the formation of biofilm, and regulating the activation of tumor necrosis factor alpha (TNF-a), transforming growth factor beta (TGF-b), interleukin 4

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Psoralen Induces Developmental Toxicity in Zebrafish Embryos/Larvae Through Oxidative Stress, Apoptosis, and Energy Metabolism Disorder

Cited by 54 publications

References 39 publications

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

Evaluation of the Developmental Toxicity Induced by E804 in Zebrafish Embryos

Toxicity Assessment of Herbal Medicine Using Zebrafish Embryos: A Systematic Review

A Review of the Pharmacological Properties of Psoralen

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