An Integrated Metabolomics-Based Model, and Identification of Potential Biomarkers, of Perfluorooctane Sulfonic Acid Toxicity in Zebrafish Embryos.

Known for their high stability and surfactant properties, per- and polyfluoroalkyl substances (PFAS) have been widely used in a range of manufactured products. Despite being largely phased out due to concerns regarding their persistence, bioaccumulation, and toxicity, legacy PFAS such as perfluorooctanesulfonic acid (PFOS) and perfluorooctanoic acid continue to persist at high levels in the environment, posing risks to aquatic organisms. We used high-resolution magic angle spinning nuclear magnetic resonance spectroscopy in intact zebrafish (Danio rerio) embryos to investigate the metabolic pathways altered by PFOS both before and after hatching (i.

High-Resolution Magic Angle Spinning (HRMAS) NMR Identifies Oxidative Stress and Impairment of Energy Metabolism by Zearalenone in Embryonic Stages of Zebrafish (), Olive Flounder () and Yellowtail Snapper ().

Zearalenone (ZEA) is a mycotoxin, commonly found in agricultural products, linked to adverse health impacts in humans and livestock. However, less is known regarding effects on fish as both ecological receptors and economically relevant "receptors" through contamination of aquaculture feeds. In the present study, a metabolomics approach utilizing high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) was applied to intact embryos of zebrafish (), and two marine fish species, olive flounder () and yellowtail snapper (), to investigate the biochemical pathways altered by ZEA exposure.

An integrated systems-level model of ochratoxin A toxicity in the zebrafish (Danio rerio) embryo based on NMR metabolic profiling.

Ochratoxin A (OTA) is one of the most widespread mycotoxin contaminants of agricultural crops. Despite being associated with a range of adverse health effects, a comprehensive systems-level mechanistic understanding of the toxicity of OTA remains elusive. In the present study, metabolic profiling by high-resolution magic angle spinning (HRMAS) NMR, coupled to intact zebrafish embryos, was employed to identify metabolic pathways in relation to a systems-level model of OTA toxicity.

Identification of apparently neurotoxic metabolites from assemblages of marine filamentous cyanobacteria associated with the intoxication of captive bottlenose dolphins (Tursiops truncatus) in the Florida Keys.

Intoxications of captive bottlenose dolphins (Tursiops truncatus) in the Florida Keys have been linked to observed interactions with marine macrophytic algal and cyanobacterial communities within enclosures. Taxonomic characterization of these communities coupled, in turn, to available observational data collected during intoxication events point to a contribution of filamentous cyanobacterial assemblages comprised of members of the polyphyletic genus, Lyngbya sensu lato. To identify toxic metabolites possibly relevant to these intoxications, chemical screening for known neurotoxins from cyanobacteria, as well as other regionally relevant harmful algal bloom (HAB) taxa, was combined with toxicity testing, and subsequent bioassay-guided fractionation, employing early life stages (i.

An integrated systems-level model of the toxicity of brevetoxin based on high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR) metabolic profiling of zebrafish embryos.

Brevetoxins (PbTx) are a well-recognized group of neurotoxins associated with harmful algal blooms, and specifically recurrent "Florida Red Tides," in marine waters that are linked to impacts on both human and ecosystem health including well-documented "fish kills" and marine mammal mortalities in affected coastal waters. Understanding mechanisms and pathways of PbTx toxicity enables identification of relevant biomarkers to better understand these environmental impacts, and improve monitoring efforts, in relation to this toxin. Toward a systems-level understanding of toxicity, and identification of potential biomarkers, high-resolution magic angle spinning nuclear magnetic resonance (HRMAS NMR) was utilized for metabolic profiling of zebrafish (Danio rerio) embryos, as an established toxicological model, exposed to PbTx-2 (the most common congener in marine waters).

Comparative toxicometabolomics of perfluorooctanoic acid (PFOA) and next-generation perfluoroalkyl substances.

Owing to environmental health concerns, a number of per- and polyfluoroalkyl substances (PFAS) have been phased-out, and increasingly replaced by various chemical analogs. Most prominent among these replacements are numerous perfluoroether carboxylic acids (PFECA). Toxicity, and environmental health concerns associated with these next-generation PFAS, however, remains largely unstudied.

Eudesmacarbonate, a Eudesmane-Type Sesquiterpene from a Marine Filamentous Cyanobacterial Mat (Oscillatoriales) in the Florida Keys.

A new, cyclic carbonate eudesmane-type sesquiterpene, eudesmacarbonate (), was isolated from marine filamentous cyanobacterial mats associated with apparent ingestion-related intoxications of captive bottlenose dolphins in the Florida Keys. Sequencing of 16S rDNA revealed that mats were composed of closely related Oscillatoriacean species including a previously undocumented species of . The structure of was elucidated by (+)-HRESIMS, 1D and 2D NMR, single-crystal X-ray diffraction, and vibrational circular dichroism data.

NMR-Based Metabolic Profiles of Intact Zebrafish Embryos Exposed to Aflatoxin B1 Recapitulates Hepatotoxicity and Supports Possible Neurotoxicity.

Aflatoxin B1 (AFB1) is a widespread contaminant of grains and other agricultural crops and is globally associated with both acute toxicity and carcinogenicity. In the present study, we utilized nuclear magnetic resonance (NMR), and specifically high-resolution magic angle spin (HRMAS) NMR, coupled to the zebrafish () embryo toxicological model, to characterize metabolic profiles associated with exposure to AFB1. Exposure to AFB1 was associated with dose-dependent acute toxicity (i.

High Incidence and Levels of Ochratoxin A in Wines Sourced from the United States.

Ochratoxin A (OTA) is one of the most prevalent mycotoxin contaminants of food crops. Among the agricultural products consequently contaminated by OTA is wine. In the present study, a sample of wines sourced from the United States was assessed for OTA.

Metabolic profiling of zebrafish (Danio rerio) embryos by NMR spectroscopy reveals multifaceted toxicity of β-methylamino-L-alanine (BMAA).

β-methylamino-L-alanine (BMAA) has been linked to several interrelated neurodegenerative diseases. Despite considerable research, specific contributions of BMAA toxicity to neurodegenerative diseases remain to be fully resolved. In the present study, we utilized state-of-the-art high-resolution magic-angle spinning nuclear magnetic resonance (HRMAS NMR), applied to intact zebrafish (Danio rerio) embryos, as a model of vertebrate development, to elucidate changes in metabolic profiles associated with BMAA exposure.

β-Cyclodextrin Attenuates Perfluorooctanoic Acid Toxicity in the Zebrafish Embryo Model.

Perfluorooctanoic acid (PFOA) has been linked to negative health outcomes including cancer, thyroid disease, infertility, and developmental delays. β-Cyclodextrin (β-CD), a cyclic sugar, has been previously shown to form strong host-guest complexes with PFOA, and is proposed as a means of environmental remediation with respect to this widespread contaminant. In the present study, β-CD was directly examined with regards to possible attenuation of the toxicity of PFOA specifically employing the zebrafish () embryo model.

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

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.

High-Resolution Magic Angle Spinning Nuclear Magnetic Resonance of Intact Zebrafish Embryos Detects Metabolic Changes Following Exposure to Teratogenic Polymethoxyalkenes from Algae.

Techniques based on nuclear magnetic resonance (NMR) for imaging and chemical analyses of in vivo, or otherwise intact, biological systems are rapidly emerging and finding diverse applications within a wide range of fields. Very recently, several NMR-based techniques have been developed for the zebrafish as a model animal system. In the current study, the novel application of high-resolution magic angle spinning (HR-MAS) NMR is presented as a means of metabolic profiling of intact zebrafish embryos.

Indole Alkaloids of the Stigonematales (Cyanophyta): Chemical Diversity, Biosynthesis and Biological Activity.

The cyanobacteria are well recognized as producers of a wide array of bioactive metabolites including toxins, and potential drug candidates. However, a limited number of taxa are generally considered with respect to both of these aspects. That said, the order Stigonematales, although largely overlooked in this regard, has become increasingly recognized as a source of bioactive metabolites relevant to both human and environmental health.

Teratogenicity of Ochratoxin A and the Degradation Product, Ochratoxin α, in the Zebrafish (Danio rerio) Embryo Model of Vertebrate Development.

Ochratoxins, and particularly ochratoxin A (OTA), are toxic fungal-derived contaminants of food and other agricultural products. Growing evidence supports the degradation of OTA by chemical, enzymatic and/or microbial means as a potential approach to remove this mycotoxin from food products. In particular, hydrolysis of OTA to ochratoxin α (OTα) and phenylalanine is the presumptive product of degradation in most cases.

A rapid method for separation and identification of microcystins using capillary electrophoresis and time-of-flight mass spectrometry.

This paper demonstrates a method for the rapid separation and identification of four microcystin (MC) variants commonly found in aquatic environments. The procedure utilizes capillary electrophoresis (CE) coupled to UV absorbance and time-of-flight mass spectrometric (TOF-MS) detectors. All four analytes were effectively separated within 6min using phosphate buffer in 50-μm ID capillaries with an applied electric field of 400V/cm.

Identification of teratogenic polymethoxy-1-alkenes from , and taxonomically diverse freshwater cyanobacteria and green algae.

is among the most commonly recognized toxigenic cyanobacteria associated with harmful algal blooms (HAB) in freshwater systems, and specifically associated with multiple water-soluble toxins. Lipophilic metabolites from , however, were previously shown to exert teratogenicity (i.e.

Indole alkaloids from Fischerella inhibit vertebrate development in the zebrafish (Danio rerio) embryo model.

Cyanobacteria are recognized producers of toxic or otherwise bioactive metabolite associated, in particular, with so-called "harmful algal blooms" (HABs) and eutrophication of freshwater systems. In the present study, two apparently teratogenic indole alkaloids from a freshwater strain of the widespread cyanobacterial genus, Fischerella (Stigonemataceae), were isolated by bioassay-guided fractionation, specifically using the zebrafish (Danio rerio) embryo, as a model of vertebrate development. The two alkaloids include the previously known 12-epi-hapalindole H isonitrile (1), and a new nitrile-containing variant, 12-epi-ambiguine B nitrile (2).

Polymethoxy-1-alkenes from Aphanizomenon ovalisporum inhibit vertebrate development in the zebrafish (Danio rerio) embryo model.

Cyanobacteria are recognized producers of a wide array of toxic or otherwise bioactive secondary metabolites. The present study utilized the zebrafish (Danio rerio) embryo as an aquatic animal model of vertebrate development to identify, purify and characterize lipophilic inhibitors of development (i.e.

Effects of cyanobacterial lipopolysaccharides from microcystis on glutathione-based detoxification pathways in the zebrafish (Danio rerio) embryo.

Cyanobacteria ("blue-green algae") are recognized producers of a diverse array of toxic secondary metabolites. Of these, the lipopolysaccharides (LPS), produced by all cyanobacteria, remain to be well investigated. In the current study, we specifically employed the zebrafish (Danio rerio) embryo to investigate the effects of LPS from geographically diverse strains of the widespread cyanobacterial genus, Microcystis, on several detoxifying enzymes/pathways, including glutathione-S-transferase (GST), glutathione peroxidase (GPx)/glutathione reductase (GR), superoxide dismutase (SOD), and catalase (CAT), and compared observed effects to those of heterotrophic bacterial (i.

Bioaccumulation of microcystins by fish associated with a persistent cyanobacterial bloom in Lago de Patzcuaro (Michoacan, Mexico).

Lago de Patzcuaro is a historically important freshwater fishery in Mexico. The lake is presently characterized by a persistent bloom of cyanobacteria, specifically dominated by recognized producers of toxic microcystins (MCYSTs). We evaluated MCYSTs in sestonic and dissolved fractions of the water column, as well as representative fish species (silversides, Chirostoma spp.

Cyanobacterial LPS potentiates cadmium toxicity in zebrafish (Danio rerio) embryos.

Cyanobacteria are prevalent in the freshwater environment, reaching critical mass in harmful algal blooms. These organisms produce a variety of toxins including endotoxins such as lipopolysaccharides (LPS), which have been previously shown to decrease glutathione-S-transferase (GST) activity in zebrafish (Danio rerio) embryos. GST plays a vital role in detoxification response during oxidative stress and provides a first line of defense after toxic heavy metal insult, before increased metallothionein expression.

First evidence of "paralytic shellfish toxins" and cylindrospermopsin in a Mexican freshwater system, Lago Catemaco, and apparent bioaccumulation of the toxins in "tegogolo" snails (Pomacea patula catemacensis).

Exposure to cyanobacterial toxins in freshwater systems, including both direct (e.g., drinking water) and indirect (e.

Toxicity of cylindrospermopsin, and other apparent metabolites from Cylindrospermopsis raciborskii and Aphanizomenon ovalisporum, to the zebrafish (Danio rerio) embryo.

Cyanobacteria produce a diverse array of toxic or otherwise bioactive compounds that pose growing threats to human and environmental health. We utilized the zebrafish (Danio rerio) embryo, as a model of vertebrate development, to investigate the inhibition of development pathways (i.e.