Carotenoid glycosides from cyanobacteria are teratogenic in the zebrafish (Danio rerio) embryo model

Abstract

Toxigenicity of cyanobacteria is widely associated with production of several well-described toxins that pose recognized threats to human and ecosystem health as part of both freshwater eutrophication, and episodic blooms in freshwater and coastal habitats. However, a preponderance of evidence indicates contribution of additional bioactive, and potentially toxic, metabolites. In the present study, the zebrafish (Danio rerio) embryo was used as a model of vertebrate development to identify, and subsequently isolate and characterize, teratogenic metabolites from two representative strains of C. raciborskii. Using this approach, three chemically related carotenoids - and specifically the xanthophyll glycosides, myxol 2′-glycoside (1), 4-ketomyxol 2′-glycoside (2) and 4-hydroxymyxol 2′-glycoside (3) - which are, otherwise, well known pigment molecules from cyanobacteria were isolated as potently teratogenic compounds. Carotenoids are recognized “pro-retinoids” with retinoic acid, as a metabolic product of the oxidative cleavage of carotenoids, established as both key mediator of embryo development and, consequently, a potent teratogen. Accordingly, a comparative toxicological study of chemically diverse carotenoids, as well as apocarotenoids and retinoids, was undertaken. Based on this, a working model of the developmental toxicity of carotenoids as pro-retinoids is proposed, and the teratogenicity of these widespread metabolites is discussed in relation to possible impacts on aquatic vertebrate populations.

Polymethoxy-1-Alkenes Screening of Chlorella and Spirulina Food Supplements Coupled with In Vivo Toxicity Studies

“…For example, selected cyanobacteria and green-algae strains have been found to produce retinoic acids and carotenoid glycosides which triggered a diverse set of teratogenic effects in the Danio rerio experimental model [27,28,43]. No Arthrospira strains were investigated for the presence of these compounds, while in the case of Chlorella genus, retinoid-like activities were only ruled out for Chlorella kessleri [27]. Therefore, in the present study, we also assessed teratogenicity using the well-established zebrafish embryo assay [44].…”

“…The aim of this study was to investigate the PMA content in commercial Chlorella and Spirulina food supplements originating from cultivations in North America, Asia and Europe as well as to evaluate the toxicity of isolated lipophilic fractions using a zebrafish Danio rerio experimental model. The toxicological screening was performed because, beside PMAs, microalgae can produce a variety of different lipophilic toxic compounds, including teratogenic retinoic acids and carotenoid glycosides [27,28]. A set of assays was employed to evaluate whether the isolated fractions of food supplements can cause teratogenicity in zebrafish embryos as well as induce oxidative stress and genotoxicity in the liver, genotoxicity in peripheral red blood cells and neurotoxicity in the brain of adult zebrafish.…”

High throughput automated detection of axial malformations in Medaka embryo

“…Finally, fishes are vertebrates and key mechanisms of embryonic development are conserved throughout evolution from fishes to human. Fish embryos are thus considered to be a relevant model for studying the impact of chemicals on human embryonic development [5] [6] and are commonly used in pharmacology and toxicology studies [7] [8]. In this study, Medaka embryos are used.…”

The Cyclodextrin-Perfluorinated Surfactant Host-Guest Complex: Fundamental Studies for Potential Environmental Remediation and Therapeutic Applications

“…To obtain embryos, zebrafish (PS strain) were reared and bred as previously described (Berry et al 2007, Jaja-Chimedza et al 2017. Briefly, adult zebrafish were maintained in 30-L tanks at 28 °C with 14 h: 10 h light/dark cycle, and bred (from approximately 10-30 individuals) above 10-L tanks in mesh enclosures.…”

“…Zebrafish embryo toxicity assays were adapted from previously described methods (Berry et al 2007, Jaja-Chimedza et al 2017. Assays were conducted in polypropylene 24-well plates (Evergreen Scientific, Los Angeles, CA) with five embryos…”