Ciguatoxins activate the Calcineurin signalling pathway in Yeasts: Potential for development of an alternative detection tool?

Ciguatoxins (CTXs) are lipid-soluble polyether compounds produced by dinoflagellates from the genus Gambierdiscus spp. typically found in tropical and subtropical zones. This endemic area is however rapidly expanding due to environmental perturbations, and both toxic Gambierdiscus spp. and ciguatoxic fishes have been recently identified in the North Atlantic Ocean (Madeira and Canary islands) and Mediterranean Sea. Ciguatoxins bind to Voltage Gated Sodium Channels on the membranes of sensory neurons, causing Ciguatera Fish Poisoning (CFP) in humans, a disease characterized by a complex array of gastrointestinal, neurological, neuropsychological, and cardiovascular symptoms. Although CFP is the most frequently reported non bacterial food-borne poisoning worldwide, there is still no simple and quick way of detecting CTXs in contaminated samples. In the prospect to engineer rapid and easy-to-use CTXs live cells-based tests, we have studied the effects of CTXs on the yeast Saccharomyces cerevisiae, a unicellular model which displays a remarkable conservation of cellular signalling pathways with higher eukaryotes. Taking advantage of this high level of conservation, yeast strains have been genetically modified to encode specific transcriptional reporters responding to CTXs exposure. These yeast strains were further exposed to different concentrations of either purified CTX or micro-algal extracts containing CTXs. Our data establish that CTXs are not cytotoxic to yeast cells even at concentrations as high as 1µM, and cause an increase in the level of free intracellular calcium in yeast cells. Concomitantly, a dose-dependent activation of the calcineurin signalling pathway is observed, as assessed by measuring the activity of specific transcriptional reporters in the engineered yeast strains. These findings offer promising prospects regarding the potential development of a yeast cells-based test that could supplement or, in some instances, replace current methods for the routine detection of CTXs in seafood products.

Influence of Motor Imagery Modality on First-Serve Performance in Tennis Players.

Motor imagery (MI) is frequently used in tennis players. This pilot study aimed to assess whether the MI modality and preference of skilled tennis players could influence their service performance when using MI before serving first balls. Twenty expert players (Mage = 18.6 years) completed the movement imagery questionnaire (third version) to assess their MI modality scores (internal visual, external visual, and kinesthetic) and their MI preference. Participants completed 4 experimental counterbalanced sessions spread over 4 weeks, each including the completion of 20 first-serve balls in match condition. The sessions included a control condition (i.e., only physical practice trials) and three MI conditions during which the players had to mentally imagine themselves performing a serve according to one of the imagery modalities, either internal visual, external visual, or kinesthetic, before serving. The percentage of success, the speed of the service balls (measured by a tablet with SWING VISION and a radar gun), and an efficiency score were recorded and then evaluated by experts and served as performance indicators and dependent variables. The results of this study showed that players benefited from MI before serving and that almost a third of the participants achieved a higher percentage of success and efficiency scores when using their preferred MI modality. These results lead us, in an applied way, to suggest to skilled tennis players to determine their MI preference and to have recourse to the mental simulation of a successful serve before serving the first balls in match condition.

First evidence of palytoxin and 42-hydroxy-palytoxin in the marine cyanobacterium Trichodesmium.

Marine pelagic diazotrophic cyanobacteria of the genus Trichodesmium (Oscillatoriales) are widespread throughout the tropics and subtropics, and are particularly common in the waters of New Caledonia. Blooms of Trichodesmium are suspected to be a potential source of toxins in the ciguatera food chain and were previously reported to contain several types of paralyzing toxins. The toxicity of water-soluble extracts of Trichodesmium spp. were analyzed by mouse bioassay and Neuroblastoma assay and their toxic compounds characterized using liquid chromatography coupled with tandem mass spectrometry techniques. Here, we report the first identification of palytoxin and one of its derivatives, 42-hydroxy-palytoxin, in field samples of Trichodesmium collected in the New Caledonian lagoon. The possible role played by Trichodesmium blooms in the development of clupeotoxism, this human intoxication following the ingestion of plankton-eating fish and classically associated with Ostreopsis blooms, is also discussed.

A review of traditional remedies of ciguatera fish poisoning in the Pacific.

Ciguatera fish poisoning (CFP) is an illness caused by eating tropical coral fish contaminated with ciguatoxins (CTXs). The clinical management of patients with CFP is generally supportive and symptomatic in nature as no antidote exists. Of the many drugs prescribed, several have been claimed to be efficient in small, uncontrolled studies, but the outcomes of treatments with these medicines are often contradictory. In New Caledonia, traditional remedies are commonly employed in the treatment of CFP and of the 90 plant species catalogued as useful in CFP, the most popular herbal remedy by far is a decoction prepared from the leaves of Heliotropium foertherianum Diane & Hilger (Boraginaceae). Other important plants used in the treatment of CFP include Euphorbia hirta L. (Euphorbiaceae) and Vitex L. sp. (Lamiaceae). This review focuses on the evidence for efficacy of these species and pharmacological studies which support their use. Other plants used in CFP and the conventional treatment of CFP are also discussed briefly.

Sulfated steroids: ptilosteroids A-C and ptilosaponosides A and B from the Solomon Islands marine sponge Ptilocaulis spiculifer.

Three new pregnanes, ptilosteroid A (1), ptilosteroid B (2), and ptilosteroid C (3), and two new pregnane glycosides, ptilosaponoside A (4) and ptilosaponoside B (5), were isolated from the marine sponge Ptilocaulis spiculifer collected in the Solomon Islands. The structures were determined by spectroscopic methods. Biological tests of these compounds showed that they are not cytotoxic against KB cells.

Antiplasmodial activities of homogentisic acid derivative protein kinase inhibitors isolated from a Vanuatu marine sponge Pseudoceratina sp.

As part of our search for new antimalarial drugs in South Pacific marine sponges, we have looked for inhibitors of Pfnek-1, a specific protein kinase of Plasmodium falciparum. On the basis of promising activity in a preliminary screening, the ethanolic crude extract of a new species of Pseudoceratina collected in Vanuatu was selected for further investigation. A bioassay-guided fractionation led to the isolation of a derivative of homogentisic acid [methyl (2,4-dibromo-3,6-dihydroxyphenyl)acetate, 4a] which inhibited Pfnek-1 with an IC(50) around 1.8 muM. This product was moderately active in vitro against a FcB1 P. falciparum strain (IC(50) = 12 muM). From the same sponge, we isolated three known compounds [11,19-dideoxyfistularin-3 (1), 11-deoxyfistularin-3 (2) and dibromo-verongiaquinol (3)] which were inactive against Pfnek-1. Synthesis and biological evaluation of some derivatives of 4a are reported.

Modulation of inducible nitric oxide synthase gene expression in RAW 264.7 murine macrophages by Pacific ciguatoxin.

To investigate the possible involvement of the nitric oxide radical (NO) in ciguatera fish poisoning (CFP), the in vitro effects of the main Pacific ciguatoxin (P-CTX-1B) and bacterial lipopolysaccharide (LPS) were comparatively studied on neuroblastoma Neuro-2a and on macrophage RAW 264.7 cell lines. NO accumulation was quantified by measuring nitrite levels in cellular supernatant using Griess reagent while the up-regulation of inducible nitric oxide synthase (iNOS) at the mRNA level was quantified via Real-Time Reverse-Transcription Polymerase Chain Reaction (RT-PCR). P-CTX-1B caused a concentration- and time-dependent induction of iNOS in RAW 264.7 cells but not in Neuro-2a cells. NO production was evidenced by increased nitrite levels in the 10 microM range after 48 h of RAW 264.7 cells exposure to LPS and P-CTX-1B (0.05 microg/ml and 6 nM, respectively). The expression of iNOS mRNA peaked at 8h for LPS then gradually decreased to low level at 48 h. In contrast, a sustained level was recorded with P-CTX-1B in the 8-48 h time interval. The addition of N(omega)-nitro-L-arginine methyl ester (L-NAME), a stereoselective NOS inhibitor, strongly diminished NO formation but had no effect on iNOS mRNA synthesis. The implication of NO in CFP paves the way for new therapies for both western and traditional medicines.

Cytotoxic Effects of Environmental Toxins on Human Glial Cells.

Toxins produced by cyanobacteria and dinoflagellates have increasingly become a public health concern due to their degenerative effects on mammalian tissue and cells. In particular, emerging evidence has called attention to the neurodegenerative effects of the cyanobacterial toxin ß-N-methylamino-L-alanine (BMAA). Other toxins such as the neurotoxins saxitoxin and ciguatoxin, as well as the hepatotoxic microcystin, have been previously shown to have a range of effects upon the nervous system. However, the capacity of these toxins to cause neurodegeneration in human cells has not, to our knowledge, been previously investigated. This study aimed to examine the cytotoxic effects of BMAA, microcystin-LR (MC-LR), saxitoxin (STX) and ciguatoxin (CTX-1B) on primary adult human astrocytes. We also demonstrated that α-lipoate attenuated MC-LR toxicity in primary astrocytes and characterised changes in gene expression which could potentially be caused by these toxins in primary astrocytes. Herein, we are the first to show that all of these toxins are capable of causing physiological changes consistent with neurodegeneration in glial cells, via oxidative stress and excitotoxicity, leading to a reduction in cell proliferation culminating in cell death. In addition, MC-LR toxicity was reduced significantly in astrocytes-treated α-lipoic acid. While there were no significant changes in gene expression, many of the probes that were altered were associated with neurodegenerative disease pathogenesis. Overall, this is important in advancing our current understanding of the mechanism of toxicity of MC-LR on human brain function in vitro, particularly in the context of neurodegeneration.

Safety, tolerability and efficacy of intradermal rabies immunization with DebioJect™.

In a single-center study, 66 healthy volunteers aged between 18 and 50years were randomized to be immunized against rabies with three different injection routes: intradermal with DebioJect™ (IDJ), standard intradermal with classical needle (IDS), also called Mantoux method, and intramuscular with classical needle (IM). "Vaccin rabique Pasteur®" and saline solution (NaCl 0.9%) were administered at D0, D7 and D28. Antigen doses for both intradermal routes were 1/5 of the dose for IM. Tolerability, safety and induced immunogenicity of IDJ were compared to IDS and IM routes. Pain was evaluated at needle insertion and at product injection for all vaccination visits. Solicited Adverse Event (SolAE) and local reactogenicity symptoms including pain, redness and pruritus were recorded daily following each vaccination visit. Adverse events (AE) were recorded over the whole duration of the study. Humoral immune response was measured by assessing the rabies virus neutralizing antibody (VNA) titers using Rapid Fluorescent Focus Inhibition Test (RFFIT). Results demonstrated that the DebioJect™ is a safe, reliable and efficient device. Significant decreases of pain at needle insertion and at vaccine injection were reported with IDJ compared to IDS and IM. All local reactogenicity symptoms (pain, redness and pruritus) after injection with either vaccine or saline solution, were similar for IDJ and IDS, except that IDJ injection induced more redness 30min after saline solution. No systemic SolAE was deemed related to DebioJect™ and classical needles. No AE was deemed related to DebioJect™. No Serious Adverse Event (SAE) was reported during the study. At the end of the study all participants were considered immunized against rabies and no significant difference in humoral response was observed between the 3 studied routes.

Antiplasmodial marine natural products in the perspective of current chemotherapy and prevention of malaria: a review.

The difficulty of obtaining an antimalarial vaccine along traditional lines, because of the highly adaptive character of the malaria parasite, prompts a ceaseless need for new drugs. To this end, marine organisms have been explored recently, as reviewed in this article within the perspective of clinically available antimalarial drugs and promising candidates. Most promising are tetrahydropyrrolo[1,2-alpha]pyrimidinium, bis-indole, and C(11)-N(5) alkaloids from sponges; pyridoacridone and decahydroquinoline alkaloids from ascidians; and pyrrole alkaloids from fungi, as well as polycyclic polyketides, norditerpene, and polyketide endoperoxides, terpene isonitriles, and, particularly, mixed-biogenesis alpha-galactosyl ceramides from sponges. The first and the latter classes of agents best fulfill the requirements for combinatorial synthesis in providing a wide variety of compounds for high-throughput screening and toxicity tests. These results came largely from nonprofit organizations, a trend that we foresee will continue. However, partnership with the pharmaceutical industry was and is needed to bring candidate drugs to the clinic. In any event, success will not be achieved without political plans to make the results of technology easily available to poor populations.

Xestospongin B, a competitive inhibitor of IP3-mediated Ca2+ signalling in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells.

Xestospongin B, a macrocyclic bis-1-oxaquinolizidine alkaloid extracted from the marine sponge Xestospongia exigua, was highly purified and tested for its ability to block inositol 1,4,5-trisphosphate (IP(3))-induced Ca(2+) release. In a concentration-dependent manner xestospongin B displaced [(3)H]IP(3) from both rat cerebellar membranes and rat skeletal myotube homogenates with an EC(50) of 44.6 +/- 1.1 microM and 27.4 +/- 1.1 microM, respectively. Xestospongin B, depending on the dose, suppressed bradykinin-induced Ca(2+) signals in neuroblastoma (NG108-15) cells, and also selectively blocked the slow intracellular Ca(2+) signal induced by membrane depolarization with high external K(+) (47 mM) in rat skeletal myotubes. This slow Ca(2+) signal is unrelated to muscle contraction, and involves IP(3) receptors. In highly purified isolated nuclei from rat skeletal myotubes, Xestospongin B reduced, or suppressed IP(3)-induced Ca(2+) oscillations with an EC(50) = 18.9 +/- 1.35 microM. In rat myotubes exposed to a Ca(2+)-free medium, Xestospongin B neither depleted sarcoplasmic reticulum Ca(2+) stores, nor modified thapsigargin action and did not affect capacitative Ca(2+) entry after thapsigargin-induced depletion of Ca(2+) stores. Ca(2+)-ATPase activity measured in skeletal myotube homogenates remained unaffected by Xestospongin B. It is concluded that xestospongin B is an effective cell-permeant, competitive inhibitor of IP(3) receptors in cultured rat myotubes, isolated myonuclei, and neuroblastoma (NG108-15) cells.

Ability of some plant extracts, traditionally used to treat ciguatera fish poisoning, to prevent the in vitro neurotoxicity produced by sodium channel activators.

The effects of 31 plant extracts, which most are traditionally used to treat ciguatera fish poisoning in the Pacific area, were studied on the cytotoxicity of mouse neuroblastoma cells produced by ouabain, veratridine and/or brevetoxin-3 or Pacific ciguatoxin-1. The cell viability was determined using a quantitative colorimetric method. A marked cytotoxicity of seven of the 31 plant extracts studied, was observed. Despite this, these plant extracts were suspected to contain active compound(s) against the cytotoxicity produced by brevetoxin (2 extracts), brevetoxin, ouabain and/or veratridine (3 extracts), or only against that of ouabain and/or veratridine (2 extracts). Among the 24 plant extracts that exhibited by themselves no cytotoxicity, 22 were active against the effect of brevetoxin or against that of both veratridine and brevetoxin. Similar results were obtained when the seven most active plant extracts were reassayed using ciguatoxin instead of brevetoxin. In conclusion, the present work reports the first activity assessment of some plant extracts, achieved in vitro on a quite large scale. The fact that 27 plant extracts were found to exert, in vitro, a protective effect against the action of ciguatoxin and/or brevetoxin, paves the way for finding new active compounds to treat ciguatera fish poisoning, provided these compounds also reverse the effects of sodium channel activators.

Structure-activity relationships of dengue antiviral polycyclic quinones.

The virucidal and antiviral photoactivities of three compounds, hypericin, tetrabromohypericin and gymnochrome B, were evaluated against dengue viruses. All the three products were active, and both the virucidal and antiviral activities were enhanced by light. Gymnochrome B was more potent than hypericin and tetrabromohypericin. The presence of the side chains on the hypericin core of gymnochromes appears to be beneficial for both virucidal and antiviral activities. This enhanced activity is likely to be linked to a complementary mechanism independent of photoactivation.

Natural-product diversity of the New Caledonian marine ecosystem compared to other ecosystems: a pharmacologically oriented view.

In comparison with other ecosystems, biodiversity and natural-product diversity of the New Caledonian marine ecosystem, comprising lagoons, barrier reefs, and deep waters in seamount regions, are described here phylogenetically with the aid of molecular drawings and tabulation of data. Admittedly, since the inception of these studies in 1977, the comparison is biased by selection of New Caledonian organisms on the basis of positive pharmacologically oriented bioassays. However, we show that these and other distortions must be accepted to draw any comparison on a regional basis, which, nonetheless, turn out to be useful for the progress of knowledge, particularly in directing future explorations of biodiversity in the search for new pharmacologically active metabolites.

Evaluation of seafood toxicity in the Australes archipelago (French Polynesia) using the neuroblastoma cell-based assay.

Ciguatera fish poisoning (CFP), a disease caused by consuming fish that have accumulated ciguatoxins (CTXs) in their tissue, is regarded as the most prevalent form of intoxication in French Polynesia. Recently, the Australes, one of the least affected archipelago until the early 1980s, has shown a dramatic increase in its incidence rates in 2009 with unusual CFP cases. In the present work, potential health hazards associated with the proliferation of various marine phytoplankton species and the consumption of fish and marine invertebrates highly popular among local population were assessed in three Australes islands: Raivavae, Rurutu and Rapa. Extracts from the marine dinoflagellates Gambierdiscus, Ostreospis and mat-forming cyanobacteria as well as fish, giant clams and sea urchin samples were examined for the presence of CTXs and palytoxin (PLTX) by using the neuroblastoma cell-based assay (CBA-N2a). Cytotoxic responses observed with both standards (Pacific CTX-3C and PLTX) and targeted marine products indicate that CBA-N2a is a robust screening tool, with high sensitivity and good repeatability and reproducibility. In Rurutu and Raivavae islands, our main findings concern the presence of CTX-like compounds in giant clams and sea urchins, suggesting a second bio-accumulation route for CFP toxins in the ciguatera food chain. In Rapa, the potential CFP risk from Gambierdiscus bloom and fish was confirmed for the first time, with levels of CTXs found above the consumer advisory level of 0.01 ng Pacific CTX-1B g(-1) of flesh in three fish samples. However, despite the presence of trace level of PLTX in Ostreopsis natural assemblages of Rapa, no sign of PLTX accumulation is yet observed in tested fish samples. Because this multi-toxinic context is likely to emerge in most French Polynesian islands, CBA-N2a shows great potential for future applications in the algal- and toxin-based field monitoring programmes currently on hand locally.

MOLECULAR CHARACTERIZATION OF THE DIVERSITY AND POTENTIAL TOXICITY OF CYANOBACTERIAL MATS IN TWO TROPICAL LAGOONS IN THE SOUTH PACIFIC OCEAN(1).

Marine benthic cyanobacteria in tropical areas have recently been associated with several human poisoning events. To enhance the characterization of these microorganisms and their potential toxicity, benthic cyanobacterial communities were sampled in the lagoons of two islands (Raivavae and Rurutu) located in French Polynesia where human poisoning events by seafood had been reported. The morphological appearance of the mats was used to identify four types of cyanobacterial mat. By a 16S rRNA sequencing approach, it appeared that these mats were usually dominated by a restricted number of operational taxonomic units (OTUs), which were closely related to Leptolyngbya, Oscillatoria, Hydrocoleum, and Anabaena sequences, as previously reported in other tropical lagoons. Interestingly, we determined that these dominant filamentous OTUs were associated in the mats with other cyanobacteria, including unicellular species. By using a population genetic approach based on the sequencing of the internally transcribed spacer (ITS) of the rRNA operon, we found a very restricted genetic diversity in the most common OTU, which displayed a high sequence similarity with Leptolyngbya sp. In addition, there was no geographic differentiation at various spatial scales in the distribution of the different genotypes, suggesting that this species is able to spread over large distances. Finally, PCR screening of genes involved in the biosynthesis of known cyanotoxins revealed the presence of the saxitoxin gene (stxG) in two mats containing a mix of filamentous and unicellular cyanobacterial species.

Protective effect of Heliotropium foertherianum (Boraginaceae) folk remedy and its active compound, rosmarinic acid, against a Pacific ciguatoxin.

ETHNOPHARMACOLOGICAL RELEVANCE: Senescent leaves of Heliotropium foertherianum Diane & Hilger (Boraginaceae) are traditionally used in the Pacific region to treat Ciguatera Fish Poisoning. This plant contains rosmarinic acid that is known for its multiple biological activities. In the present study, H. foertherianum aqueous extract, rosmarinic acid and its derivatives were evaluated for their capacity to reduce the effect of ciguatoxins. MATERIALS AND METHODS: Aqueous extract of H. foertherianum leaves was prepared and studied for its effects against a Pacific ciguatoxin (P-CTX-1B) in the neuroblastoma cell assay and the receptor binding assay. Rosmarinic acid and six derivatives were also evaluated by means of these bioassays. For this purpose, we have developed an improved synthetic route for caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE). RESULTS: Both the aqueous extract of H. foertherianum leaves and rosmarinic acid showed inhibitory activities against a Pacific ciguatoxin in the above bioassays. Among all the molecules that were evaluated, rosmarinic acid was the most active compound. CONCLUSION: These results confirm further the potential of H. foertherianum in the treatment of Ciguatera Fish Poisoning.

Aqueous extract of Vitex trifolia L. (Labiatae) inhibits LPS-dependent regulation of inflammatory mediators in RAW 264.7 macrophages through inhibition of Nuclear Factor kappa B translocation and expression.

ETHNOPHARMACOLOGICAL RELEVANCE: Vitex trifolia L. (Labiatae), a widespread tree found from the Asia-Pacific to the east Africa regions is used in the traditional medicine of the Pacific islands to treat inflammatory-associated conditions. AIM OF THE STUDY: We herein evaluated its in vitro regulatory effects on the expression profile of lipopolysaccharide (LPS)-induced inflammatory genes focusing on regulation of chemokines C-X-C motif 10 (CXCL-10) and C-C motif ligand 3 (CCL-3) and cyclo-oxygenase (COX)-2. Furthermore, the plant effect on the LPS-mediated activation of Nuclear Factor kappa B (NF-κB) was also studied. MATERIALS AND METHODS: Aqueous extract of Vitex trifolia leaves was prepared and evaluated for its effect on LPS-induced stress and toxicity-related genes in RAW 264.7 macrophage cells using RT(2) Profiler Polymerase Chain Reaction (PCR) Array System. Effects of the extract on LPS-induced chemokines CCL-3 and CXCL-10, COX-2, and NF-κB p50 and p65 mRNA levels were also studied using Reverse Transcription quantitative PCR (RT-qPCR) technique. Translocation of the nuclear factor was further assessed by measuring its nuclear p65 subunit via an ELISA-based TransAM method. RESULTS: Vitex trifolia extract at 5000µg/ml exerted a significant inhibitory effect on the expression of various LPS-induced inflammatory genes in RAW 264.7 cells after 8h of incubation time. Using RT-qPCR, this anti-inflammatory effect was further confirmed by significant inhibition of CCL-3 and CXCL-10 mRNA production in LPS-stimulated RAW 264.7 cells upon treatment with 2500µg/ml of Vitex trifolia extract. Furthermore, the inhibitory activity of this plant on LPS-induced COX-2 mRNA was also observed at a concentration of 2500µg/ml in a time-dependent manner. TransAM assays showed that LPS-induced NF-κB translocation was also inhibited by Vitex trifolia extract even at a concentration of extract as low as 250µg/ml. RT-qPCR assays showed that aqueous extract of Vitex trifolia leaves had a significant inhibitory activity on LPS-induced p50 mRNA synthesis. Interestingly, however, no effect on p65 subunit mRNA expression was observed. Moreover, PCR array analysis showed that LPS-induced inflammatory and apoptosis genes under NF-κB control are also repressed by the extract. CONCLUSION: The anti-inflammatory properties of Vitex trifolia extract seem associated with inhibition of NF-κB translocation through a reduction in the expression level of NF-κB p50 but interestingly not p65 subunit mRNA. The regulatory effects of Vitex trifolia on NF-κB and consequently on inflammation mediators such as chemokines CCL-3 and CXCL-10, and COX-2 provide new evidence of its efficacy and emphasise its high potential therapeutic value. However, further in vivo experiments are still required to validate its utilization as a remedy against inflammatory diseases.

Detection of ciguatoxin-like and paralysing toxins in Trichodesmium spp. from New Caledonia lagoon.

Marine pelagic cyanobacteria Trichodesmium are widespread in the New Caledonia lagoon. Blooms of these Oscillatoriales are suspected to be a potential source of toxins in the ciguatera food chain and were previously reported to contain certain types of paralysing toxins. In the present study, toxicity experiments were conducted on lipid- and water-soluble extracts of freeze-dried samples of these cyanobacteria. Lipid-soluble fractions revealed a ciguatoxin-like activity in both in vivo (mouse bioassay) and in vitro (mouse neuroblastoma cells assay and receptor binding assay using tritiated brevetoxin-3) assays. The water-soluble fractions tested on mice exhibited neurotoxicity with paralytic symptoms. These toxicities have also been observed with benthic filamentous cyanobacteria within the Oscillatoriales order, also collected in New Caledonia. This study provides an unprecedented evidence of the toxicity of Trichodesmium species from the New Caledonia lagoon. This survey also demonstrates the possible role of these cyanobacteria in ciguatera fish poisoning.

First identification of the neurotoxin homoanatoxin-a from mats of Hydrocoleum lyngbyaceum (marine cyanobacterium) possibly linked to giant clam poisoning in New Caledonia.

We report the first identification of homoanatoxin-a from benthic marine cyanobacteria (Hydrocoleum lyngbyaceum) samples collected in Lifou (Loyalty Islands, New Caledonia), where cases of giant clams (Tridacna maxima) intoxications were recorded during a severe ciguatera fish poisoning outbreak. Homoanatoxin-a was also detected in extracts of giant clams harvested in the surroundings of the contaminated area suggesting the possible link between these poisoning events and the occurrence of potentially neurotoxic Hydrocoleum.