title: 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.
authors.affiliation: Department of Chemistry and Biochemistry, Marine Science Program, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA. Electronic address: ajaja001@fiu.edu.
authors.forename: Asha
authors.initials: A
authors.lastname: Jaja-Chimedza
authors.affiliation: Department of Biological Sciences, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. Electronic address: ksanc023@fiu.edu.
authors.forename: Kristel
authors.initials: K
authors.lastname: Sanchez
authors.affiliation: Department of Biological Sciences, Florida International University, 11200 SW 8th Street, Miami, FL 33199, USA. Electronic address: gantarm@fiu.edu.
authors.forename: Miroslav
authors.initials: M
authors.lastname: Gantar
authors.affiliation: Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33146, USA. Electronic address: pgibbs@rsmas.miami.edu.
authors.forename: Patrick
authors.initials: P
authors.lastname: Gibbs
authors.affiliation: Department of Marine Biology and Ecology, Rosenstiel School of Marine and Atmospheric Sciences, University of Miami, 4600 Rickenbacker Causeway, Miami, FL 33146, USA. Electronic address: mschmale@rsmas.miami.edu.
authors.forename: Michael
authors.initials: M
authors.lastname: Schmale
authors.affiliation: Department of Chemistry and Biochemistry, Marine Science Program, Florida International University, 3000 NE 151st Street, North Miami, FL 33181, USA. Electronic address: berryj@fiu.edu.
authors.forename: John P
authors.initials: JP
authors.lastname: Berry
mesh_terms: D000818:Animals; D002338:Carotenoids / Q000633:toxicity*; D000458:Cyanobacteria / Q000737:chemistry; D004625:Embryo, Nonmammalian / Q000187:drug effects; D047108:Embryonic Development / Q000187:drug effects; D005068:Eutrophication; D005618:Fresh Water; D006027:Glycosides / Q000633:toxicity*; D013723:Teratogens / Q000633:toxicity*; D014212:Tretinoin; D014874:Water Pollutants, Chemical / Q000633:toxicity*; D015027:Zebrafish
chemical_list: D006027:Glycosides; D013723:Teratogens; D014874:Water Pollutants, Chemical; D002338:Carotenoids; D014212:Tretinoin
keywords: Carotenoid; Cyanobacteria; Myxoxanthophyll; Retinoid; Teratogenicity; Zebrafish