Liver genomic responses to ciguatoxin: evidence for activation of Phase I and Phase II detoxification pathways following an acute hypothermic response in mice

Ciguatoxins (CTX) are polyether neurotoxins that target voltage-gated sodium channels and are responsible for ciguatera, the most common fish-borne food poisoning in humans. This study characterizes the global transcriptional response of mouse liver to a symptomatic dose (0.26 ng/g) of the highly potent Pacific ciguatoxin-1 (P-CTX-1). At 1 h post-exposure 2.4% of features on a 44K whole genome array were differentially expressed (p ≤ 0.0001), increasing to 5.2% at 4 h and decreasing to 1.4% by 24 h post-CTX exposure. Data were filtered (|fold change| ≥ 1.5 and p ≤ 0.0001 in at least one time point) and a trend set of 1550 genes were used for further analysis. Early gene expression was likely influenced prominently by an acute 4°C decline in core body temperature by 1 h, which resolved by 8 h following exposure. An initial downregulation of 32 different solute carriers, many involved in sodium transport, was observed. Differential gene expression in pathways involving eicosanoid biosynthesis and cholesterol homeostasis was also noted. Cytochrome P450s (Cyps) were of particular interest due to their role in xenobiotic metabolism. Twenty-seven genes, mostly members of Cyp2 and Cyp4 families, showed significant changes in expression. Many Cyps underwent an initial downregulation at 1 h but were quickly and strongly upregulated at 4 and 24 h post-exposure. In addition to Cyps, increases in several glutathione S-transferases were observed, an indication that both phase I and phase II metabolic reactions are involved in the hepatic response to CTX in mice

Large-scale sea turtle mortality events in El Salvador attributed to paralytic shellfish toxin-producing algae blooms

A fines de octubre y principios de noviembre de 2013 y 2017, cientos de tortugas marinas fueron encontradas muertas a lo largo de la costa del Pacífico de El Salvador. Las tortugas muertas estaban en buenas condiciones corporales y no tenían ninguna lesión u otras anomalías importantes. A fin de determinar el papel de las toxinas paralíticas de los mariscos (PST) en esta mortalidad masiva, muestras de tejido, incluidos los contenidos de sangre, flipper, hígado, riñón, estómago e intestinos, de tortugas verdes muertas tortugas (Chelonia mydas) y tortugas lora (Lepidochelys olivacea) fueron analizadas para PST usando un ensayo de unión a receptor radioactivo, ensayo inmunoabsorbente ligado a enzimas, y cromatografía líquida de alto rendimiento. Los valores más altos de PST se detectaron en contenido entérico en el evento de 2013 (7,304.1 μg STX eq kg − 1) y en contenido gástrico durante el evento de 2017 (16,165.0 μg STX eq kg − 1). Durante estos eventos, sensaciones remotas. Las imágenes de clorofila-a y de altura de línea de fluorescencia revelaron anomalías sugestivas de algas Florece frente a la costa de El Salvador. En el evento de 2017, Pyrodinium bahamense fue observado en muestras de contenido gastrointestinal de tortugas marinas afectadas. También se analizó la región donde se encontraron tortugas marinas muertas, pero los productores de saxitoxinas especies se encontraron en baja abundancia (5400 cell / L en 2013 y 672 cell / L en 2017), que puede reflejar muestreo limitado. Aunque los niveles umbrales de toxicidad en las especies de tortugas marinas no están bien caracterizada, nuestra evidencia sugiere que estos grandes eventos fueron el resultado de las floraciones de algas que producen PST y que estas floraciones son la mayor causa de mortalidad de tortugas marinas en esta región

Gene expression profiling in brain of mice exposed to the marine neurotoxin ciguatoxin reveals an acute anti-inflammatory, neuroprotective response

<p>Abstract</p> <p>Background</p> <p>Ciguatoxins (CTXs) are polyether marine neurotoxins and potent activators of voltage-gated sodium channels. This toxin is carried by multiple reef-fish species and human consumption of ciguatoxins can result in an explosive gastrointestinal/neurologic illness. This study characterizes the global transcriptional response in mouse brain to a symptomatic dose of the highly toxic Pacific ciguatoxin P-CTX-1 and additionally compares this data to transcriptional profiles from liver and whole blood examined previously. Adult male C57/BL6 mice were injected with 0.26 ng/g P-CTX-1 while controls received only vehicle. Animals were sacrificed at 1, 4 and 24 hrs and transcriptional profiling was performed on brain RNA with Agilent whole genome microarrays. RT-PCR was used to independently validate gene expression and the web tool DAVID was used to analyze gene ontology (GO) and molecular pathway enrichment of the gene expression data.</p> <p>Results</p> <p>A pronounced 4°C hypothermic response was recorded in these mice, reaching a minimum at 1 hr and lasting for 8 hrs post toxin exposure. Ratio expression data were filtered by intensity, fold change and p-value, with the resulting data used for time course analysis, K-means clustering, ontology classification and KEGG pathway enrichment. Top GO hits for this gene set included acute phase response and mono-oxygenase activity. Molecular pathway analysis showed enrichment for complement/coagulation cascades and metabolism of xenobiotics. Many immediate early genes such as Fos, Jun and Early Growth Response isoforms were down-regulated although others associated with stress such as glucocorticoid responsive genes were up-regulated. Real time PCR confirmation was performed on 22 differentially expressed genes with a correlation of 0.9 (Spearman's Rho, p < 0.0001) with microarray results.</p> <p>Conclusions</p> <p>Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against neuroinflammation. Pathologic activity of the complement/coagulation cascade has been shown in patients suffering from a chronic form of ciguatera poisoning and is of particular interest in this model. Anti-inflammatory processes were at work not only in the brain but were also seen in whole blood and liver of these animals, creating a systemic anti-inflammatory environment to protect against the initial cellular damage caused by the toxin.</p

Ciguatoxin occurrence in food-web components of a Cuban Coral Reef Ecosystem: Risk-assessment implications

In Cuba, ciguatera poisoning associated with fish consumption is the most commonly occurring non-bacterial seafood-borne illness. Risk management through fish market regulation has existed in Cuba for decades and consists of bans on selected species above a certain weight; however, the actual occurrence of ciguatoxins (CTXs) in seafood has never been verified. From this food safety risk management perspective, a study site locally known to be at risk for ciguatera was selected. Analysis of the epiphytic dinoflagellate community identified the microalga Gambierdiscus. Gambierdiscus species included six of the seven species known to be present in Cuba (G. caribaeus, G. belizeanus, G. carpenteri, G. carolinianus, G. silvae, and F. ruetzleri). CTX-like activity in invertebrates, herbivorous and carnivorous fishes were analyzed with a radioligand receptor-binding assay and, for selected samples, with the N2A cell cytotoxicity assay. CTX activity was found in 80% of the organisms sampled, with toxin values ranging from 2 to 8 ng CTX3C equivalents g−1 tissue. Data analysis further confirmed CTXs trophic magnification. This study constitutes the first finding of CTX-like activity in marine organisms in Cuba and in herbivorous fish in the Caribbean. Elucidating the structure–activity relationship and toxicology of CTX from the Caribbean is needed before conclusions may be drawn about risk exposure in Cuba and the wider Caribbean.info:eu-repo/semantics/publishedVersio

Methylmercury contamination in Mediterranean seafood: Exposure assessment and cost of illness implications

Methylmercury (MeHg) is a widespread contaminant that bioaccumulates in marine food webs, including those in the Mediterranean sea. It poses serious health risks, especially to developing infants and children, where exposure can cause neurological damage and developmental delays. In addition to health concerns, high MeHg levels in seafood can lead to economic losses through cognitive impairments that reduce productivity. Despite seafood being a dietary staple in Mediterranean countries, the full extent of MeHg's health and economic impacts remains underexplored, especially with the rising international trade. This study aims to (a) estimate MeHg exposures in Mediterranean populations from consumption of Mediterranean seafood and (b) quantify the economic costs associated with MeHg intake. We assessed population exposures in Mediterranean countries by combining a highly granular seafood supply data on Aquatic Resource Trade in Species (ARTIS), alongside Global Dietary Database (GDD) and review of MeHg levels in Mediterranean seafood. The economic cost was then derived by linking MeHg intake to productivity losses associated with cognitive deficits. As a result, we estimate that Mediterranean countries experience over €10 billion in annual economic losses due to IQ-related productivity decline associated with MeHg exposure from consuming seafood sourced from various fishing areas of the Mediterranean Sea. The novelty of this research lies in its transdisciplinary approach to MeHg impact assessment that incorporates highly detailed seafood supply data with dietary surveys, and scientific literature to provide a more realistic and detailed view of MeHg exposures and the associated cost-of illness from local seafood consumption accross Mediterranean countries. These findings highlight a critical aspect of MeHg management: while international trade can mitigate local exposure by providing access to less-contaminated imports, it simultaneously exports the contamination burden to other regions. This duality emphasizes the importance of global cooperation in addressing seafood safety and managing transboundary MeHg risks

Risques pour la santé humaine liés aux proliférations d’Ostreopsis spp. sur le littoral basque : Avis révisé de l’Anses : Rapport d’expertise collective

244 pagesL’Anses a été saisie le 3 décembre 2021 par la Direction générale de la santé (DGS) et la Direction générale de l’alimentation (DGAL) pour la réalisation de l’expertise suivante dont le titre initial était : « demande d'avis relatif aux risques liés aux efflorescences d'Ostreopsis spp. sur l’ensemble du littoral français

Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells

Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and β-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for ciguatera

Linking ciguatera poisoning to spatial ecology of fish: A novel approach to examining the distribution of biotoxin levels in the great barracuda by combining non-lethal blood sampling and biotelemetry

Ciguatera in humans is typically caused by the consumption of reef fish that have accumulated Ciguatoxins (CTXs) in their flesh. Over a six month period, we captured 38 wild adult great barracuda (Sphyraena barracuda), a species commonly associated with ciguatera in The Bahamas. We sampled three tissues (i.e.,muscle, liver, and blood) and analysed them for the presence of ciguatoxins using a functional in vitro N2A bioassay. Detectable concentrations of ciguatoxins found in the three tissue types ranged from 2.51 to 211.74 pg C-CTX-1 equivalents/ g. Blood and liver toxin concentrations were positively correlated (ρ=0.86, P=0.003), indicating that, for the first time, blood sampling provides a non-lethal method of detecting ciguatoxin in wild fish. Non-lethal blood sampling also presents opportunities to couple this approachwith biotelemetry and biologging techniques that enable the study of fish distribution and movement. To demonstrate the potential for linking ciguatoxin occurrencewith barracuda spatial ecology,we also present a proof-of-concept case studywhere blood samples were obtained from 20 fish before releasing them with acoustic transmitters and tracking them in the coastal waters using a fixed acoustic telemetry array covering 44 km2. Fish that tested positive for CTX may have smaller home ranges than non-toxic fish (median distance travelled, U=2.21, P=0.03). Results presented from this study may help identify high risk areas and source-sink dynamics of toxins, potentially reducing the incidence and human health risk of ciguatera fish poisoning. Moreover, development of the non-lethal sampling approach and measurement of ciguatera fromblood provide future opportunities to understand the mechanistic relationship between toxins and the spatial ecology of a broad range of marine fish species