ArticleToxicological sciences : an official journal of the Society of Toxicology2016
Comparative Developmental Toxicity of Flavonoids Using an Integrative Zebrafish System.
Article in Toxicological sciences : an official journal of the Society of Toxicology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 45 citations in OpenAlex.
- Structure-Activity Relationship of Flavonol O-Methylation Revealed by In Vitro, In Silico and Zebrafish Neurodegeneration Models.International journal of molecular sciences · 2026Article
- Peripheral neuroprotective potential and toxicological profile of fascaplysin in zebrafish models.Anatomy & cell biology · 2025Article
- Evaluation of the Inhibitory Potential of Apigenin and Related Flavonoids on Various Proteins Associated with Human Diseases Using AutoDock.International journal of molecular sciences · 2025Article
- Toxicity Assessment of Biogenic Gold Nanoparticles on Crop Seeds and Zebrafish Embryos: Implications for Agricultural and Aquatic Ecosystems.ACS omega · 2025Article
- Sea buckthorn flavonoids and their derivatives: potential natural compounds for the treatment of diabetic cardiomyopathy.Frontiers in pharmacology · 2025Review
- Developmental toxicity and estrogenic activity of antimicrobial phenolic-branched fatty acids usingFrontiers in toxicology · 2024Article
- Brain targeted luteolin-graphene oxide nanoparticle abrogates polyethylene terephthalate induced altered neurological response in zebrafish.Molecular biology reports · 2023Article
- TRAIL-Sensitizing Effects of Flavonoids in Cancer.International journal of molecular sciences · 2023Review
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- Grouping of chemicals into mode of action classes by automated effect pattern analysis using the zebrafish embryo toxicity test.Archives of toxicology · 2022Article
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- Truncation of the otoferlin transmembrane domain alters the development of hair cells and reduces membrane docking.Molecular biology of the cell · 2021Article
- Zebrafish as a Useful Model to Study Oxidative Stress-Linked Disorders: Focus on Flavonoids.Antioxidants (Basel, Switzerland) · 2021Review
- Developmental toxicity in zebrafish (Danio rerio) exposed to uranium: A comparison with lead, cadmium, and iron.Environmental pollution (Barking, Essex : 1987) · 2021Article
- Zebrafish as a Successful Animal Model for Screening Toxicity of Medicinal Plants.Plants (Basel, Switzerland) · 2020Review
- The Coming Age of Flavonoids in the Treatment of Diabetic Complications.Journal of clinical medicine · 2020Review
- Article
- Autologous cord blood in children with cerebral palsy: a review.International journal of molecular sciences · 2019Review
- Flavonoids as Prospective Neuroprotectants and Their Therapeutic Propensity in Aging Associated Neurological Disorders.Frontiers in aging neuroscience · 2019Review
- Associations Between Behavioral Effects of Bisphenol A and DNA Methylation in Zebrafish Embryos.Frontiers in genetics · 2019Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Flavonoids are a large, structurally diverse class of bioactive naturally occurring chemicals commonly detected in breast milk, soy based infant formulas, amniotic fluid, and fetal cord blood. The potential for pervasive early life stage exposures raises concerns for perturbation of embryogenesis, though developmental toxicity and bioactivity information is limited for many flavonoids. Therefore, we evaluated a suite of 24 flavonoid and flavonoid-like chemicals using a zebrafish embryo-larval toxicity bioassay-an alternative model for investigating developmental toxicity of environmentally relevant chemicals. Embryos were exposed to 1-50 µM of each chemical from 6 to 120 h postfertilization (hpf), and assessed for 26 adverse developmental endpoints at 24, 72, and 120 hpf. Behavioral changes were evaluated in morphologically normal animals at 24 and 72 hpf, at 120 hpf using a larval photomotor response (LPR) assay. Gene expression was comparatively evaluated for all compounds for effects on biomarker transcripts indicative of AHR (cyp1a) and ER (cyp19a1b, esr1, lhb, vtg) pathway bioactivity. Overall, 15 of 24 flavonoids elicited adverse effects on one or more of the developmental or behavioral endpoints. Hierarchical clustering and principle component analyses compared toxicity profiles and identified 3 distinct groups of bioactive flavonoids. Despite robust induction of multiple estrogen-responsive biomarkers, co-exposure with ER and GPER antagonists did not ameliorate toxicity, suggesting ER-independence and alternative modes of action. Taken together, these studies demonstrate that development is sensitive to perturbation by bioactive flavonoids in zebrafish that are not related to traditional estrogen receptor mode of action pathways. This integrative zebrafish platform provides a useful framework for evaluating flavonoid developmental toxicity and hazard prioritization.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.