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Sample records for ciguatoxins

  1. An investigation into ciguatoxin bioaccumulation in sharks.

    Science.gov (United States)

    Meyer, Lauren; Capper, Angela; Carter, Steve; Simpfendorfer, Colin

    2016-09-01

    Ciguatoxins (CTXs) produced by benthic Gambierdiscus dinoflagellates, readily biotransform and bioaccumulate in food chains ultimately bioconcentrating in high-order, carnivorous marine species. Certain shark species, often feeding at, or near the top of the food-chain have the ability to bioaccumulate a suite of toxins, from both anthropogenic and algal sources. As such, these apex predators are likely sinks for CTXs. This assumption, in conjunction with anecdotal knowledge of poisoning incidents, several non-specific feeding trials whereby various terrestrial animals were fed suspect fish flesh, and a single incident in Madagascar in 1994, have resulted in the widespread acceptance that sharks may accumulate CTXs. This prompted a study to investigate original claims within the literature, as well as investigate CTX bioaccumulation in the muscle and liver of 22 individual sharks from nine species, across four locations along the east coast of Australia. Utilizing an updated ciguatoxin extraction method with HPLC-MS/MS, we were unable to detect P-CTX-1, P-CTX-2 or P-CTX-3, the three primary CTX congeners, in muscle or liver samples. We propose four theories to address this finding: (1) to date, methods have been optimized for teleost species and may not be appropriate for elasmobranchs, or the CTXs may be below the limit of detection; (2) CTX may be biotransformed into elasmobranch-specific congeners as a result of unique metabolic properties; (3) 22 individuals may be an inadequate sample size given the rare occurrence of high-order ciguatoxic organisms and potential for CTX depuration; and (4) the ephemeral nature and inconsistent toxin profiles of Gambierdiscus blooms may have undermined our classifications of certain areas as CTX hotspots. These results, in combination with the lack of clarity within the literature, suggest that ciguatoxin bioaccumulation in sharks remains elusive, and warrants further investigation to determine the dynamics of toxin production

  2. Multiple ciguatoxins present in Indian Ocean reef fish.

    Science.gov (United States)

    Hamilton, Brett; Hurbungs, Mira; Jones, Alun; Lewis, Richard J

    2002-09-01

    Optimised gradient reversed-phase high-performance liquid chromatography electrospray ionisation mass spectrometry (LC/MS) methods, in combination with a [3H]-brevetoxin binding assay (RLB), revealed multiple ciguatoxins in a partially purified extract of a highly toxic Lutjanus sebae (red emperor) from the Indian Ocean. Two major ciguatoxins of 1140.6 Da (I-CTX-1 and -2) and two minor ciguatoxins of 1156.6 Da (I-CTX-3 and -4) were identified. Accurate mass analysis revealed that I-CTX-1 and -2 and Caribbean C-CTX-1 had indistinguishable masses (1140.6316 Da, at 0.44 ppm resolution). Toxicity estimated from LC/MS/RLB responses indicated that I-CTX-1 and -2 were both approximately 60% the potency of Pacific ciguatoxin-1 (P-CTX-1). In contrast to ciguatoxins of the Pacific where the more oxidised ciguatoxins are more potent, I-CTX-3 and -4 were approximately 20% of P-CTX-1 potency. Interconversion in dilute acid or on storage, typical of spiroketal and hemiketal functionality found in P-CTXs and C-CTXs, respectively, was not observed to occur between I-CTX-1 and -2. The ratio of CTX-1 and -2 varied depending on the fish extract being analysed. These results suggest that I-CTX-1 and -2 may arise from separate dinoflagellate precursors that may be oxidatively biotransformed to I-CTX-3 and -4 in fish.

  3. Preparation of anti-ciguatoxin monoclonal antibodies using synthetic haptens: sandwich ELISA detection of ciguatoxins.

    Science.gov (United States)

    Tsumuraya, Takeshi; Fujii, Ikuo; Hirama, Masahiro

    2014-01-01

    Ciguatera fish poisoning (CFP) is a form of food poisoning caused by the consumption of fish that have accumulated a type of sodium channel activator toxin called ciguatoxins (CTXs), which are produced by dinoflagellates of the genus Gambierdiscus through the food chain. CFP affects more than 50000 people each year. The extremely low level of CTXs in tainted fish has hampered the development of antibodies for the detection of these toxins. Monoclonal antibodies (mAbs) specific against major congeners of CTX3C, 51-hydroxyCTX3C, CTX1B, and 54-deoxyCTX1B were prepared by immunization of mice with protein conjugates of rationally designed synthetic haptens in place of the natural toxins. We found that haptenic groups possessing a surface area larger than 400 angstroms2 were required to produce mAbs that can bind strongly to CTXs. Direct sandwich ELISA utilizing two different monoclonal antibodies that bind specifically to one of the two wings of a CTX were established to detect CTXs. No cross-reactivity was observed against the other marine toxins tested, including brevetoxin A, brevetoxin B, okadaic acid, and maitotoxin.

  4. Fluorescent Receptor Binding Assay for Detecting Ciguatoxins in Fish

    Science.gov (United States)

    Hardison, D. Ransom; Holland, William C.; McCall, Jennifer R.; Bourdelais, Andrea J.; Baden, Daniel G.; Darius, H. Taiana; Chinain, Mireille; Tester, Patricia A.; Shea, Damian; Flores Quintana, Harold A.; Morris, James A.; Litaker, R. Wayne

    2016-01-01

    Ciguatera fish poisoning is an illness suffered by > 50,000 people yearly after consumption of fish containing ciguatoxins (CTXs). One of the current methodologies to detect ciguatoxins in fish is a radiolabeled receptor binding assay (RBA(R)). However, the license requirements and regulations pertaining to radioisotope utilization can limit the applicability of the RBA(R) in certain labs. A fluorescence based receptor binding assay (RBA(F)) was developed to provide an alternative method of screening fish samples for CTXs in facilities not certified to use radioisotopes. The new assay is based on competition binding between CTXs and fluorescently labeled brevetoxin-2 (BODIPY®- PbTx-2) for voltage-gated sodium channel receptors at site 5 instead of a radiolabeled brevetoxin. Responses were linear in fish tissues spiked from 0.1 to 1.0 ppb with Pacific ciguatoxin-3C (P-CTX-3C) with a detection limit of 0.075 ppb. Carribean ciguatoxins were confirmed in Caribbean fish by LC-MS/MS analysis of the regional biomarker (C-CTX-1). Fish (N = 61) of six different species were screened using the RBA(F). Results for corresponding samples analyzed using the neuroblastoma cell-based assay (CBA-N2a) correlated well (R2 = 0.71) with those of the RBA(F), given the low levels of CTX present in positive fish. Data analyses also showed the resulting toxicity levels of P-CTX-3C equivalents determined by CBA-N2a were consistently lower than the RBA(F) affinities expressed as % binding equivalents, indicating that a given amount of toxin bound to the site 5 receptors translates into corresponding lower cytotoxicity. Consequently, the RBA(F), which takes approximately two hours to perform, provides a generous estimate relative to the widely used CBA-N2a which requires 2.5 days to complete. Other RBA(F) advantages include the long-term (> 5 years) stability of the BODIPY®- PbTx-2 and having similar results as the commonly used RBA(R). The RBA(F) is cost-effective, allows high sample

  5. Fluorescent Receptor Binding Assay for Detecting Ciguatoxins in Fish.

    Science.gov (United States)

    Hardison, D Ransom; Holland, William C; McCall, Jennifer R; Bourdelais, Andrea J; Baden, Daniel G; Darius, H Taiana; Chinain, Mireille; Tester, Patricia A; Shea, Damian; Quintana, Harold A Flores; Morris, James A; Litaker, R Wayne

    2016-01-01

    Ciguatera fish poisoning is an illness suffered by > 50,000 people yearly after consumption of fish containing ciguatoxins (CTXs). One of the current methodologies to detect ciguatoxins in fish is a radiolabeled receptor binding assay (RBA(R)). However, the license requirements and regulations pertaining to radioisotope utilization can limit the applicability of the RBA(R) in certain labs. A fluorescence based receptor binding assay (RBA(F)) was developed to provide an alternative method of screening fish samples for CTXs in facilities not certified to use radioisotopes. The new assay is based on competition binding between CTXs and fluorescently labeled brevetoxin-2 (BODIPY®-PbTx-2) for voltage-gated sodium channel receptors at site 5 instead of a radiolabeled brevetoxin. Responses were linear in fish tissues spiked from 0.1 to 1.0 ppb with Pacific ciguatoxin-3C (P-CTX-3C) with a detection limit of 0.075 ppb. Carribean ciguatoxins were confirmed in Caribbean fish by LC-MS/MS analysis of the regional biomarker (C-CTX-1). Fish (N = 61) of six different species were screened using the RBA(F). Results for corresponding samples analyzed using the neuroblastoma cell-based assay (CBA-N2a) correlated well (R2 = 0.71) with those of the RBA(F), given the low levels of CTX present in positive fish. Data analyses also showed the resulting toxicity levels of P-CTX-3C equivalents determined by CBA-N2a were consistently lower than the RBA(F) affinities expressed as % binding equivalents, indicating that a given amount of toxin bound to the site 5 receptors translates into corresponding lower cytotoxicity. Consequently, the RBA(F), which takes approximately two hours to perform, provides a generous estimate relative to the widely used CBA-N2a which requires 2.5 days to complete. Other RBA(F) advantages include the long-term (> 5 years) stability of the BODIPY®-PbTx-2 and having similar results as the commonly used RBA(R). The RBA(F) is cost-effective, allows high sample

  6. Ciguatoxins: Cyclic Polyether Modulators of Voltage-gated Iion Channel Function

    Directory of Open Access Journals (Sweden)

    Richard J. Lewis

    2006-04-01

    Full Text Available Ciguatoxins are cyclic polyether toxins, derived from marine dinoflagellates, which are responsible for the symptoms of ciguatera poisoning. Ingestion of tropical and subtropical fin fish contaminated by ciguatoxins results in an illness characterised by neurological, cardiovascular and gastrointestinal disorders. The pharmacology of ciguatoxins is characterised by their ability to cause persistent activation of voltage-gated sodium channels, to increase neuronal excitability and neurotransmitter release, to impair synaptic vesicle recycling, and to cause cell swelling. It is these effects, in combination with an action to block voltage-gated potassium channels at high doses, which are believed to underlie the complex of symptoms associated with ciguatera. This review examines the sources, structures and pharmacology of ciguatoxins. In particular, attention is placed on their cellular modes of actions to modulate voltage-gated ion channels and other Na+-dependent mechanisms in numerous cell types and to current approaches for detection and treatment of ciguatera.

  7. Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells.

    Directory of Open Access Journals (Sweden)

    César Mattei

    Full Text Available 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 beta-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.

  8. Bioavailability and intravenous toxicokinetic parameters for Pacific ciguatoxin P-CTX-1 in rats.

    Science.gov (United States)

    Ledreux, Aurélie; Ramsdell, John S

    2013-03-15

    Ciguatoxins are sodium channel activator toxins responsible for ciguatera fish poisoning. In this study, we determined the toxicokinetic parameters of the Pacific ciguatoxin P-CTX-1 in rats after an intravenous (iv) dose of 0.13 ng P-CTX-1 per g of body weight. The ciguatoxin activity was assessed over time in blood using the sensitive functional Neuro2a assay. The data were analyzed with a two-compartmental model. After exposure, the ciguatoxin activity exhibited a rapid (alpha half-life of 6 min) and extensive distribution into tissues (apparent steady state volume of distribution of 7.8 L). Ciguatoxin elimination from blood was slower with a beta half-life estimated at 35.5 h. The toxicokinetic parameters determined from this study were compared to data previously obtained after oral and intraperitoneal exposure of rats to 0.26 ng P-CTX-1 per g of body weight. Maximal bioavailability was determined by the area under the concentration curve, and was used to calculate the absolute P-CTX-1 bioavailabilities for oral and intraperitoneal routes of exposures of 39% and 75%, respectively.

  9. Use of two detection methods to discriminate ciguatoxins from brevetoxins: application to great barracuda from Florida Keys.

    Science.gov (United States)

    Dechraoui, M-Yasmine Bottein; Tiedeken, Jessica A; Persad, Renuka; Wang, Zhihong; Granade, H Ray; Dickey, Robert W; Ramsdell, John S

    2005-09-01

    In Florida (USA), numerous cases of human ciguatera fish poisoning, as well as neurotoxic shellfish poisoning following consumption of local seafood products, have been reported. By using in parallel, the sodium channel receptor binding assay (RBA), and the ouabain/veratridine-dependent cytotoxicity assay (N2A assay), we established criteria to identify, detect, and quantify ciguatoxins in fish extracts, with a brevetoxin as internal standard. Results showed that the Caribbean ciguatoxin C-CTX-1 exhibited an 8-fold higher potency in the RBA than brevetoxins and, a 440 and 2300-fold higher potency in the N2A assay than PbTx-1 and PbTx-3, respectively. Moreover, a sensitivity comparison between assays revealed that the N2A assay was more sensitive (12-fold) for ciguatoxin analysis, whereas the RBA was more sensitive (3-24-fold) for brevetoxins analysis. Based on the relative potency between toxins and the opposite sensitivity of both assays we have used the RBA and the N2A assay to screen great barracuda (Sphyraena barracuda) collected from the Florida Keys for ciguatoxins and brevetoxins. Fish extract analysis showed a sodium channel-dependent activity consistent with the presence of ciguatoxins, and not brevetoxins. Among 40 barracudas analyzed, 60% contained ciguatoxin levels in their liver measurable by the N2A assay with the most toxic fish containing 2.1ppb C-CTX-1 equivalents.

  10. A Multidisciplinary Study of Ciguatoxin and Related Low Molecular Weight Toxins from Marine Sources

    Science.gov (United States)

    1989-08-01

    atrial and taenia cecum assays. Results and Discussion Table 1 summarizes the results of several species of fishes obtained in 1986-87 from the DLNR and... taenia caecum and compared to those of cultured Gambierdiscus toxicus and "pure" ciguatoxin (CTX). With the exception of CTX, maitotoxin (MTX) and all...the taenia caecum and depression of perivascular nerve-mediated (PVS) inhibitory response, at low frequencies for C. strigosus and at all frequencies

  11. A Multidisciplinary Study of Ciguatoxin and Related Low Molecular Weight Toxins from Marine Source

    Science.gov (United States)

    1986-08-01

    contraction. Effect of reserpine In these experiments the guinea-pigs were pretreated with reserpine (i.p., 2 mg/kg) for two days to deplete their neuronal ...467-473. Scheuer, P.J., Takahashi, W., Tsutsumi, J. and Yoshida, T. (1967). Ciguatoxin: Isolation and chemical nature. Science 21: 1267-1268. Yas• moto ... Diseases Atten: SGRD-UIZ-M Fort Detrick, Frederick, MD 21701-5011 1 copy Coimaander US Army Medical Research and Development Command Atten: SGRD-RMI-S Fort

  12. Chronic ciguatoxin treatment induces synaptic scaling through voltage gated sodium channels in cortical neurons.

    Science.gov (United States)

    Martín, Víctor; Vale, Carmen; Rubiolo, Juan A; Roel, Maria; Hirama, Masahiro; Yamashita, Shuji; Vieytes, Mercedes R; Botana, Luís M

    2015-06-15

    Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long-term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate receptor expression in order to stabilize the overall activity. Immediate early genes, such as Arc and Egr1, are induced in response to activity changes and underlie the trafficking of glutamate receptors during neuronal homeostasis. To better understand the long lasting neurological consequences of ciguatera, it is important to establish the role that chronic changes in activity produced by ciguatoxins represent to central neurons. Here, the effect of a 30 min exposure of 10-13 days in vitro (DIV) cortical neurons to the synthetic ciguatoxin CTX 3C on Arc and Egr1 expression was evaluated using real-time polymerase chain reaction approaches. Since the toxin increased the mRNA levels of both Arc and Egr1, the effect of CTX 3C in NaV channels, membrane potential, firing activity, miniature excitatory postsynaptic currents (mEPSCs), and glutamate receptors expression in cortical neurons after a 24 h exposure was evaluated using electrophysiological and western blot approaches. The data presented here show that CTX 3C induced an upregulation of Arc and Egr1 that was prevented by previous coincubation of the neurons with the NaV channel blocker tetrodotoxin. In addition, chronic CTX 3C caused a concentration-dependent shift in the activation voltage of NaV channels to more negative potentials and produced membrane potential depolarization. Moreover, 24 h treatment of cortical neurons with 5 nM CTX 3C decreased neuronal firing and induced synaptic scaling mechanisms, as evidenced by a decrease in the amplitude of mEPSCs and downregulation in the protein level of glutamate receptors that was also prevented by tetrodotoxin

  13. Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1.

    Science.gov (United States)

    Inserra, Marco C; Israel, Mathilde R; Caldwell, Ashlee; Castro, Joel; Deuis, Jennifer R; Harrington, Andrea M; Keramidas, Angelo; Garcia-Caraballo, Sonia; Maddern, Jessica; Erickson, Andelain; Grundy, Luke; Rychkov, Grigori Y; Zimmermann, Katharina; Lewis, Richard J; Brierley, Stuart M; Vetter, Irina

    2017-02-22

    Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1-1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1.8, while the slope factor of the conductance-voltage curves was significantly increased for NaV1.7 and peak current was significantly increased for NaV1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of NaV1.8 and the tetrodotoxin-sensitive isoforms NaV1.7 and NaV1.6, respectively. The contribution of these isoforms to excitability of peripheral C- and A-fibre sensory neurons, confirmed using murine skin and visceral single-fibre recordings, reflects the expression pattern of NaV isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation.

  14. Pacific ciguatoxins in food web components of coral reef systems in the Republic of Kiribati.

    Science.gov (United States)

    Mak, Yim Ling; Wai, Tak-Cheung; Murphy, Margaret B; Chan, Wing Hei; Wu, Jia Jun; Lam, James C W; Chan, Leo L; Lam, Paul K S

    2013-12-17

    Ciguatera fish poisoning (CFP) is a foodborne illness caused by consumption of coral reef fishes contaminated by ciguatoxins (CTXs); of the known CTX congeners, the Pacific ciguatoxins (P-CTXs) are the most toxic. Little is known about the trophodynamics of P-CTXs in coral reef systems. The present study explores the distribution, transfer, and trophic magnification of P-CTX-1, -2, and -3 in coral reef systems with high (ciguatoxic) and low (reference) ciguatoxicity in a CFP-endemic nation by use of liquid chromatography-tandem mass spectrometry (LC-MS/MS). In ciguatoxic coral reef systems, P-CTXs were detected in 54% of herbivorous fishes [total P-CTXs <0.500-1670 pg/g wet weight (ww)], 72% of omnivorous fishes (<0.500-1810 pg/g ww), and 76% of carnivorous fishes (<0.500-69 500 pg/g ww), as well as a lobster ( Panulirus penicillatus ; 2.36 pg/g ww) and an octopus (Octopodidae; 2.56 pg/g ww). The dominant P-CTXs in grazers and piscivorous fishes were P-CTX-2 and -1, respectively. No significant correlation between P-CTX levels and lipid content in three target predatory fishes indicated that accumulation of P-CTXs does not depend on fat content. A weak but significant positive relationship was observed between δ(15)N and P-CTX-1 levels, but further investigation is required to confirm its biomagnification potential.

  15. Multiple sodium channel isoforms mediate the pathological effects of Pacific ciguatoxin-1

    Science.gov (United States)

    Inserra, Marco C.; Israel, Mathilde R.; Caldwell, Ashlee; Castro, Joel; Deuis, Jennifer R.; Harrington, Andrea M.; Keramidas, Angelo; Garcia-Caraballo, Sonia; Maddern, Jessica; Erickson, Andelain; Grundy, Luke; Rychkov, Grigori Y.; Zimmermann, Katharina; Lewis, Richard J.; Brierley, Stuart M.; Vetter, Irina

    2017-01-01

    Human intoxication with the seafood poison ciguatoxin, a dinoflagellate polyether that activates voltage-gated sodium channels (NaV), causes ciguatera, a disease characterised by gastrointestinal and neurological disturbances. We assessed the activity of the most potent congener, Pacific ciguatoxin-1 (P-CTX-1), on NaV1.1–1.9 using imaging and electrophysiological approaches. Although P-CTX-1 is essentially a non-selective NaV toxin and shifted the voltage-dependence of activation to more hyperpolarising potentials at all NaV subtypes, an increase in the inactivation time constant was observed only at NaV1.8, while the slope factor of the conductance-voltage curves was significantly increased for NaV1.7 and peak current was significantly increased for NaV1.6. Accordingly, P-CTX-1-induced visceral and cutaneous pain behaviours were significantly decreased after pharmacological inhibition of NaV1.8 and the tetrodotoxin-sensitive isoforms NaV1.7 and NaV1.6, respectively. The contribution of these isoforms to excitability of peripheral C- and A-fibre sensory neurons, confirmed using murine skin and visceral single-fibre recordings, reflects the expression pattern of NaV isoforms in peripheral sensory neurons and their contribution to membrane depolarisation, action potential initiation and propagation. PMID:28225079

  16. Preliminary Study on Extraction and Purification of Ciguatoxin%雪卡毒素的提取纯化方法初步研究

    Institute of Scientific and Technical Information of China (English)

    闫鸿鹏; 张彩霞; 赵肃清; 张焜

    2012-01-01

    Ciguatoxin is a kind of neurotoxic marine algal toxins. However, ciguatoxin in high purity is the material foundation for related research. In this paper, ciguatoxin was extracted from Epinephelussp liver and purified by Florisil and Sephadex LH-20 chromatography. Furthermore, this ciguatoxin was identified as Pacific ciguatoxin (P-CTX-1) by high-performance liquid chromatography/mass spectrometry (HPLC/ MS) and cytotoxicity assay. This ciguatoxin has the same retention time comparing to the reference compound P-CTX-1 in HPLC. The mass spectra of this ciguatoxin showed the mass peaks of 1 111. 3 ([M + H]+) and 1 133.0 ([M+Na]+) , which was fully consistent with the reported mass peaks of P-CTX-1. The cytotoxicity of ciguatoxin on the human neuroblastoma cell(SK-N-SH )was determined by MTT assay, and the results indicated a linear dose-dependent inhibition effect of ciguatoxin on proliferation of the cells. The cytotoxicity assay further confirmed it as ciguatoxin in high purity.%雪卡毒素(ciguatoxin)是一类具有神经毒性的海洋藻类毒素,高纯度雪卡毒素是开展其相关研究的物质基础.以石斑鱼肝脏为原料,对其脂溶性粗提物经Florisil柱和Sephadex LH-20柱纯化后,用高效液相色谱/质谱(HPLC/MS)和细胞毒性方法对其进行鉴定,证明为太平洋雪卡毒素(P-CTX-1).HPLC鉴定分析提取物与太平洋雪卡毒素(P-CTX-1)具有相同的保留时间.HPLC/MS检测表明纯化样品在m/z=1 111.3和m/z=1 133.0处出现雪卡毒素[M+H]+峰和[M+Na]+峰,与已有的P-CTX-1分子离子峰完全吻合.四甲基偶氮唑蓝法(MTT)细胞毒性试验证明了雪卡毒素样品对入神经母细胞瘤(SK-N-SH)具有毒性作用,毒素剂量与细胞生长抑制率成线性关系.细胞毒性试验进一步确认该提取物为雪卡毒素,且纯度较高.

  17. Release of neuropeptides from a neuro-cutaneous co-culture model: A novel in vitro model for studying sensory effects of ciguatoxins.

    Science.gov (United States)

    Le Garrec, Raphaele; L'herondelle, Killian; Le Gall-Ianotto, Christelle; Lebonvallet, Nicolas; Leschiera, Raphael; Buhe, Virginie; Talagas, Matthieu; Vetter, Irina; Lewis, Richard J; Misery, Laurent

    2016-06-15

    Ciguatoxins are the major toxins responsible for ciguatera fish poisoning, a disease dominated by muco-cutaneous sensory disorders including paresthesiae, cold dysesthesia and pruritus. While the ciguatoxins are well known to target voltage-gated sodium channels (VGSCs), the ensuing molecular mechanisms underlying these sensory disorders remain poorly understood. In this study, we propose a primary sensory neuron-keratinocyte co-culture as an appropriate model to study the neuro-cutaneous effects of ciguatoxins. Using this model, we show for the first time that nanomolar concentrations of Pacific ciguatoxin-2 (P-CTX-2) induced a VGSC-dependent release of substance P (SP) and calcitonin gene-related peptide (CGRP). As these neuropeptides are known mediators of pain and itch sensations, the ciguatoxin-induced sensory disturbances in ciguatera fish poisoning may involve the release of these neuropeptides. We further determined time- and P-CTX-2 concentration-dependence of the release of SP and CGRP from the co-culture model. Moreover, we highlighted the influence of extracellular calcium on the release of neuropeptides elicited by P-CTX-2. These findings underline the usefulness of this novel in vitro model for studying the cellular and molecular mechanisms of the neuro-cutaneous effects of ciguatoxins, which may assist with identifying potential therapeutics for ciguatera fish poisoning.

  18. Damage and detection techniques of ciguatoxins%西加毒素的危害及其检测技术

    Institute of Scientific and Technical Information of China (English)

    孙娟

    2011-01-01

    Ciguatoxins is a kind of terrible coral fish toxin produced by certain marine benthic microalgae and may accumulate in various kinds of coral fishes through the food chain. It result in poisoning in those who eat coral fish containing ciguatoxins. In recent years, as coral fishes are increasingly traded among many countries and areas , it has become a world health problem. In order to prevent food poisoning induced by ciguatoxins , its molecular structure , chemical properties, original biological resource, poisoning mechanism, clinical symptoms and the hazard to humans were summarized. Besides, the detection analytical techniques of ciguatoxins are described and compared in detail.%西加毒素是由少数几种海洋底栖微藻产生,具有极强毒性的生物毒素,它能够通过食物链传递而累计在多种珊瑚鱼体内,继而造成人类因食用鱼类而中毒.近年来,随着珊瑚鱼类在世界范围内的广泛贸易,西加毒素中毒已经成为全球性的健康问题.为给预防西加毒素引起的食物中毒提供借鉴,对西加毒素的分子结构、化学性质、生物来源、制毒机理、中毒症状和对人类的危害进行了综述.就目前主要的检测方法进行了技术特性的介绍,并对常用检测方法的优缺点进行了比较分析.

  19. Rapid Extraction and Identification of Maitotoxin and Ciguatoxin-Like Toxins from Caribbean and Pacific Gambierdiscus Using a New Functional Bioassay

    Science.gov (United States)

    Lewis, Richard J.; Inserra, Marco; Vetter, Irina; Holland, William C.; Hardison, D. Ransom; Tester, Patricia A.; Litaker, R. Wayne

    2016-01-01

    Background Ciguatera is a circumtropical disease produced by polyether sodium channel toxins (ciguatoxins) that enter the marine food chain and accumulate in otherwise edible fish. Ciguatoxins, as well as potent water-soluble polyethers known as maitotoxins, are produced by certain dinoflagellate species in the genus Gambierdiscus and Fukuyoa spp. in the Pacific but little is known of the potential of related Caribbean species to produce these toxins. Methods We established a simplified procedure for extracting polyether toxins from Gambierdiscus and Fukuyoa spp. based on the ciguatoxin rapid extraction method (CREM). Fractionated extracts from identified Pacific and Caribbean isolates were analysed using a functional bioassay that recorded intracellular calcium changes (Ca2+) in response to sample addition in SH-SY5Y cells. Maitotoxin directly elevated Ca2+i, while low levels of ciguatoxin-like toxins were detected using veratridine to enhance responses. Results We identified significant maitotoxin production in 11 of 12 isolates analysed, with 6 of 12 producing at least two forms of maitotoxin. In contrast, only 2 Caribbean isolates produced detectable levels of ciguatoxin-like activity despite a detection limit of >30 pM. Significant strain-dependent differences in the levels and types of ciguatoxins and maitotoxins produced by the same Gambierdiscus spp. were also identified. Conclusions The ability to rapidly identify polyether toxins produced by Gambierdiscus spp. in culture has the potential to distinguish ciguatoxin-producing species prior to large-scale culture and in naturally occurring blooms of Gambierdiscus and Fukuyoa spp. Our results have implications for the evaluation of ciguatera risk associated with Gambierdiscus and related species. PMID:27467390

  20. Developmental toxicity and molecular responses of marine medaka (Oryzias melastigma) embryos to ciguatoxin P-CTX-1 exposure.

    Science.gov (United States)

    Yan, Meng; Leung, Priscilla T Y; Ip, Jack C H; Cheng, Jin-Ping; Wu, Jia-Jun; Gu, Jia-Rui; Lam, Paul K S

    2017-02-10

    Ciguatoxins are produced by toxic benthic dinoflagellates and cause ciguatera fish poisoning worldwide, but the toxic effects on developing marine fish have not been well investigated. The Pacific ciguatoxin (P-CTX-1), is a potent sodium channel agonist, which is one of the most toxic members among all CTXs. This study evaluated the toxic effects of microinjecting purified Pacific ciguatoxin-1 (P-CTX-1) on embryonic development of marine medaka Oryzias melastigma. A lower 96h-LD50 value was estimated for eleuthero-embryos (1.32ngg(-1)) than that for embryos (1.71ngg(-1)), indicating that P-CTX-1 is more lethal to newly hatched medaka larvae. P-CTX-1 induced detrimental effects during embryonic development, including hatching failure, abnormalities in physical development (caudal fin malformation and spinal deformities), internal damage (green coloration of the gall bladder and hemorrhaging), immune dysfunction, and altered muscle physiology (bradycardia and hyperkinetic twitching). The results of a transcriptional expression analysis of genes related to the stress/immune responses, cardiac and bone development, and apoptosis supported the observed developmental abnormalities. This study advanced the understanding of P-CTX-1 mediated toxic mechanisms in the development of early life stages of a fish, and thus contributed to the toxicity assessment of CTXs in marine ecosystems.

  1. Involvement of both sodium influx and potassium efflux in ciguatoxin-induced nodal swelling of frog myelinated axons.

    Science.gov (United States)

    Mattei, César; Molgó, Jordi; Benoit, Evelyne

    2014-10-01

    Ciguatoxins, mainly produced by benthic dinoflagellate Gambierdiscus species, are responsible for a complex human poisoning known as ciguatera. Previous pharmacological studies revealed that these toxins activate voltage-gated Na+ channels. In frog nodes of Ranvier, ciguatoxins induce spontaneous and repetitive action potentials (APs) and increase axonal volume that may explain alterations of nerve functioning in intoxicated humans. The present study aimed determining the ionic mechanisms involved in Pacific ciguatoxin-1B (P-CTX-1B)-induced membrane hyperexcitability and subsequent volume increase in frog nodes of Ranvier, using electrophysiology and confocal microscopy. The results reveal that P-CTX-1B action is not dependent on external Cl- ions since it was not affected by substituting Cl- by methylsulfate ions. In contrast, substitution of external Na+ by Li+ ions suppressed spontaneous APs and prevented nodal swelling. This suggests that P-CTX-1B-modified Na+ channels are not selective to Li+ ions and/or are blocked by these ions, and that Na+ influx through Na+ channels opened during spontaneous APs is required for axonal swelling. The fact that the K+ channel blocker tetraethylammonium modified, but did not suppress, spontaneous APs and greatly reduced nodal swelling induced by P-CTX-1B indicates that K+ efflux might also be involved. This is supported by the fact that P-CTX-1B, when tested in the presence of both tetraethylammonium and the K+ ionophore valinomycin, produced the characteristic nodal swelling. It is concluded that, during the action of P-CTX-1B, water movements responsible for axonal swelling depend on both Na+ influx and K+ efflux. These results pave the way for further studies regarding ciguatera treatment.

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

    OpenAIRE

    Kumar-Roine, Shilpa; Matsui, Mariko,; Chinain, M.; Laurent, Dominique; Pauillac, S.

    2008-01-01

    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 qu...

  3. First Report of Ciguatoxins in Two Starfish Species: Ophidiaster ophidianus and Marthasterias glacialis

    Science.gov (United States)

    Silva, Marisa; Rodriguez, Inés; Barreiro, Aldo; Kaufmann, Manfred; Neto, Ana Isabel; Hassouani, Meryem; Sabour, Brahim; Alfonso, Amparo; Botana, Luis M.; Vasconcelos, Vitor

    2015-01-01

    Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs). These phycotoxins are produced mainly by dinoflagellates that belong to the genus Gambierdiscus that are transformed in more toxic forms in predatory fish guts, and are more present in the Indo-Pacific and Caribbean areas. It is estimated that CFP causes per year more than 10,000 intoxications worldwide. With the rise of water temperature and anthropogenic intervention, it is important to study the prevalence of CFP in more temperate waters. Through inter- and subtidal sampling, 22 species of organisms were collected, in Madeira and Azores archipelagos and in the northwestern Moroccan coast, during September of 2012 and June and July of 2013. A total of 94 samples of 22 different species of bivalves, gastropods, echinoderms and crustaceans where analyzed by Ultra Performance Liquid Chromatography-Mass Spectometry-Ion Trap-Time of Flight (UPLC-MS-IT-TOF) and Ultra Performance Chromatography- Mass Spectrometry (UPLC-MS). Our main aim was to detect new vectors and ascertain if there were some geographical differences. We detected for the first time putative CTXs in echinoderms, in two starfish species—M. glacialis and O. ophidianus. We detected differences regarding uptake values by organisms and geographical location. Toxin amounts were significant, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, in order to better access human health risk. In addition, we suggest monitoring of these toxins should be extended to other vectors, starfish being a good alternative for protecting and accessing human health risk. PMID:26402702

  4. Ciguatera fish poisoning in Hong Kong--a 10-year perspective on the class of ciguatoxins.

    Science.gov (United States)

    Wong, Chun-Kwan; Hung, Patricia; Lo, Janice Y C

    2014-08-01

    The present study used liquid chromatography-tandem mass spectrometry (LC-MS/MS) to investigate retrospectively ciguatoxin (CTX)-positive samples as determined by mouse bioassay (MBA) in the past 10 years in Hong Kong. The results showed that Pacific CTXs (P-CTX-1, -2 and -3) were the most commonly observed toxins found in the samples, indicating Pacific Ocean areas as the most important origin of ciguatera fish poisoning. Clinical diagnosis from ciguatera patients also revealed the predominance of neurological illnesses in most cases, supporting intoxication of Pacific origin. This study demonstrated the ability of laboratory analysis to identify and quantify Pacific CTXs in suspected fish samples, so as to support the clinical diagnosis of ciguatera. Comparative analysis (Student's t-test and Spearman's rank correlation analysis) on the two CTX detection methods showed approximate linearity for overall P-CTXs (P-CTX-1, -2 and -3)/P-CTX-1 alone as derived by LC-MS/MS and total toxicity levels (P-CTX-1 equivalent) as determined by MBA. The LC-MS/MS method coupled with the rapid extraction method could allow the detection of trace amount of CTXs at levels below the clinically relevant limit, 0.1 ppb P-CTX-1 in fish flesh. For practical application, the adoption of a two-tiered approach for testing, chemical analysis by LC-MS/MS for toxic fish screening, coupled with biological assay by MBA for final toxicity confirmation, was proposed for first-line screening of CTX in potentially contaminated fish samples in the market, with an aim to minimizing the use of laboratory mice and at the same time providing reasonably effective means for routine analysis.

  5. Simultaneous quantification of Pacific ciguatoxins in fish blood using liquid chromatography-tandem mass spectrometry.

    Science.gov (United States)

    Mak, Yim Ling; Wu, Jia Jun; Chan, Wing Hei; Murphy, Margaret B; Lam, James C W; Chan, Leo L; Lam, Paul K S

    2013-04-01

    Ciguatera fish poisoning (CFP) is a food intoxication caused by exposure to ciguatoxins (CTXs) in coral reef fish. Rapid analytical methods have been developed recently to quantify Pacific-CTX-1 (P-CTX-1) in fish muscle, but it is destructive and can cause harm to valuable live coral reef fish. Also fish muscle extract was complex making CTX quantification challenging. Not only P-CTX-1, but also P-CTX-2 and P-CTX-3 could be present in fish, contributing to ciguatoxicity. Therefore, an analytical method for simultaneous quantification of P-CTX-1, P-CTX-2, and P-CTX-3 in whole blood of marketed coral reef fish using sonication, solid-phase extraction (SPE), and liquid chromatography tandem mass spectrometry (LC-MS/MS) was developed. The optimized method gave acceptable recoveries of P-CTXs (74-103 %) in fish blood. Matrix effects (6-26 %) in blood extracts were found to be significantly reduced compared with those in muscle extracts (suppressed by 34-75 % as reported in other studies), thereby minimizing potential for false negative results. The target P-CTXs were detectable in whole blood from four coral reef fish species collected in a CFP-endemic region. Similar trends in total P-CTX levels and patterns of P-CTX composition profiles in blood and muscle of these fish were observed, suggesting a relationship between blood and muscle levels of P-CTXs. This optimized method provides an essential tool for studies of P-CTX pharmacokinetics and pharmacodynamics in fish, which are needed for establishing the use of fish blood as a reliable sample for the assessment and control of CFP.

  6. First Report of Ciguatoxins in Two Starfish Species: Ophidiaster ophidianus and Marthasterias glacialis.

    Science.gov (United States)

    Silva, Marisa; Rodriguez, Inés; Barreiro, Aldo; Kaufmann, Manfred; Isabel Neto, Ana; Hassouani, Meryem; Sabour, Brahim; Alfonso, Amparo; Botana, Luis M; Vasconcelos, Vitor

    2015-09-21

    Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs). These phycotoxins are produced mainly by dinoflagellates that belong to the genus Gambierdiscus that are transformed in more toxic forms in predatory fish guts, and are more present in the Indo-Pacific and Caribbean areas. It is estimated that CFP causes per year more than 10,000 intoxications worldwide. With the rise of water temperature and anthropogenic intervention, it is important to study the prevalence of CFP in more temperate waters. Through inter- and subtidal sampling, 22 species of organisms were collected, in Madeira and Azores archipelagos and in the northwestern Moroccan coast, during September of 2012 and June and July of 2013. A total of 94 samples of 22 different species of bivalves, gastropods, echinoderms and crustaceans where analyzed by Ultra Performance Liquid Chromatography-Mass Spectometry-Ion Trap-Time of Flight (UPLC-MS-IT-TOF) and Ultra Performance Chromatography- Mass Spectrometry (UPLC-MS). Our main aim was to detect new vectors and ascertain if there were some geographical differences. We detected for the first time putative CTXs in echinoderms, in two starfish species-M. glacialis and O. ophidianus. We detected differences regarding uptake values by organisms and geographical location. Toxin amounts were significant, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, in order to better access human health risk. In addition, we suggest monitoring of these toxins should be extended to other vectors, starfish being a good alternative for protecting and accessing human health risk.

  7. Acute Exposure to Pacific Ciguatoxin Reduces Electroencephalogram Activity and Disrupts Neurotransmitter Metabolic Pathways in Motor Cortex.

    Science.gov (United States)

    Kumar, Gajendra; Au, Ngan Pan Bennett; Lei, Elva Ngai Yu; Mak, Yim Ling; Chan, Leanne Lai Hang; Lam, Michael Hon Wah; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-09-10

    Ciguatera fish poisoning (CFP) is a common human food poisoning caused by consumption of ciguatoxin (CTX)-contaminated fish affecting over 50,000 people worldwide each year. CTXs are classified depending on their origin from the Pacific (P-CTXs), Indian Ocean (I-CTXs), and Caribbean (C-CTXs). P-CTX-1 is the most toxic CTX known and the major source of CFP causing an array of neurological symptoms. Neurological symptoms in some CFP patients last for several months or years; however, the underlying electrophysiological properties of acute exposure to CTXs remain unknown. Here, we used CTX purified from ciguatera fish sourced in the Pacific Ocean (P-CTX-1). Delta and theta electroencephalography (EEG) activity was reduced remarkably in 2 h and returned to normal in 6 h after a single exposure. However, second exposure to P-CTX-1 induced not only a further reduction in EEG activities but also a 2-week delay in returning to baseline EEG values. Ciguatoxicity was detected in the brain hours after the first and second exposure by mouse neuroblastoma assay. The spontaneous firing rate of single motor cortex neuron was reduced significantly measured by single-unit recording with high spatial resolution. Expression profile study of neurotransmitters using targeted profiling approach based on liquid chromatography-tandem mass spectrometry revealed an imbalance between excitatory and inhibitory neurotransmitters in the motor cortex. Our study provides a possible link between the brain oscillations and neurotransmitter release after acute exposure to P-CTX-1. Identification of EEG signatures and major metabolic pathways affected by P-CTX-1 provides new insight into potential biomarker development and therapeutic interventions.

  8. First Report of Ciguatoxins in Two Starfish Species: Ophidiaster ophidianus and Marthasterias glacialis

    Directory of Open Access Journals (Sweden)

    Marisa Silva

    2015-09-01

    Full Text Available Ciguatera fish poisoning (CFP is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs. These phycotoxins are produced mainly by dinoflagellates that belong to the genus Gambierdiscus that are transformed in more toxic forms in predatory fish guts, and are more present in the Indo-Pacific and Caribbean areas. It is estimated that CFP causes per year more than 10,000 intoxications worldwide. With the rise of water temperature and anthropogenic intervention, it is important to study the prevalence of CFP in more temperate waters. Through inter- and subtidal sampling, 22 species of organisms were collected, in Madeira and Azores archipelagos and in the northwestern Moroccan coast, during September of 2012 and June and July of 2013. A total of 94 samples of 22 different species of bivalves, gastropods, echinoderms and crustaceans where analyzed by Ultra Performance Liquid Chromatography-Mass Spectometry-Ion Trap-Time of Flight (UPLC-MS-IT-TOF and Ultra Performance Chromatography- Mass Spectrometry (UPLC-MS. Our main aim was to detect new vectors and ascertain if there were some geographical differences. We detected for the first time putative CTXs in echinoderms, in two starfish species—M. glacialis and O. ophidianus. We detected differences regarding uptake values by organisms and geographical location. Toxin amounts were significant, showing the importance and the need for continuity of these studies to gain more knowledge about the prevalence of these toxins, in order to better access human health risk. In addition, we suggest monitoring of these toxins should be extended to other vectors, starfish being a good alternative for protecting and accessing human health risk.

  9. Development of a monoclonal antibody against the left wing of ciguatoxin CTX1B: thiol strategy and detection using a sandwich ELISA.

    Science.gov (United States)

    Tsumuraya, Takeshi; Takeuchi, Katsutoshi; Yamashita, Shuji; Fujii, Ikuo; Hirama, Masahiro

    2012-09-01

    Ciguatera fish poisoning (CFP) is a form of food poisoning caused by the ingestion of a variety of reef fish that have accumulated trace amounts of ciguatoxins produced by dinoflagellates of the genus Gambierdiscus through the food chain. CFP affects more than 50,000 people each year. The extremely low level of the causative neurotoxins, ciguatoxins, in fish has hampered the preparation of antibodies for detecting the toxins. In this paper, we describe a thiol strategy for synthesizing a keyhole limpet hemocyanin (KLH)-conjugate (20) of the ABCDE-ring fragment of the Pacific ciguatoxins, CTX1B (1) and 54-deoxyCTX1B (4). We succeeded in producing a monoclonal antibody (3G8) against the left wings of these ciguatoxins by immunizing mice with the hapten-KLH conjugate (20) as the synthetic antigen. The most promising mAb, 3G8, does not cross-react with other related marine toxins. Sandwich enzyme-linked immunosorbent assay (ELISA) utilizing 3G8 and the previously prepared monoclonal antibody (8H4) enabled us to detect 1 specifically at less than 0.28 ng/mL.

  10. Prevalence of ciguatoxins in lionfish (Pterois spp.) from Guadeloupe, Saint Martin, and Saint Barthélmy Islands (Caribbean).

    Science.gov (United States)

    Soliño, Lucía; Widgy, Saha; Pautonnier, Anthony; Turquet, Jean; Loeffler, Christopher R; Flores Quintana, Harold A; Diogène, Jorge

    2015-08-01

    Lionfish (Pterois spp.) are invasive species that have recently spread throughout the Caribbean. Lionfish are available for purchase in local markets for human consumption in several islands of the region. We examined the prevalence of ciguatoxins (CTXs) in lionfish from the French Antilles, a ciguatera-endemic region. The neuroblastoma-2a (N2a) cell assay was used to assess composite cytotoxicity in 120 fish samples collected from the surrounding waters of Guadeloupe (n = 60), Saint Barthélemy Islands (n = 55) and Saint Martin (n = 5). Twenty-seven of these samples exhibited CTX-like activity by the N2a assay. Ciguatoxin (CTX) was confirmed by liquid chromatography-tandem mass spectrometry (LC-MS/MS) in multiple samples that presented highest composite toxicity levels by N2a. Those fish found to contain CTXs were all from Saint Barthélemy. Lionfish from Guadeloupe and Saint Martin did not exhibit toxin activity, although the sample size from Saint Martin was insufficient to draw any conclusions as to the incidence of CTXs. In this study, we provide information about the potential hazard of ciguatera associated with the consumption of lionfish from known endemic areas. We also demonstrate the utility of the cell-based assay combined with LC-MS/MS to assess activity and to provide structural confirmation of CTXs respectively.

  11. 雪卡毒素人工抗原合成及鉴定%Synthesis and identification of artificial antigen of ciguatoxin

    Institute of Scientific and Technical Information of China (English)

    张彩霞; 闫鸿鹏; 赵肃清; 张焜; 周丽华

    2011-01-01

    Ciguatoxin was a kind of marine toxin exists in coral fish. A trace residual might lead to ciguatera poisoning. In order to build an immunochromatography assay method,it was necessary to synthesize artificial antigen of ciguatoxin firstly. Monensin,an analogue of ciguatoxin,was reconstructed to succinyl monensin through the reaction between succinic anhydride and monensin,and then coupled to bovine serum albumin(BSA)and ovalbumin(OVA)by mixed acid anhydride method to synthesize the artificial antigen MON-HS-BSA and MON-HS-OVA. The antibodies against ciguatoxin were raised in serum of MON-HS-BSA immunized BalB/c mice by indirect competitive ELISA. The above results showed that the artificial antigen of ciguatoxin was synthesized successfully and it could be used to develop monoclonal antibodies against ciguatoxin in the future.%雪卡毒素是一种存在于珊瑚鱼中的海洋毒素,极低剂量就会引起中毒。为了建立雪卡毒素的免疫分析方法,必须合成其人工抗原才能制备抗体。以雪卡毒素的结构类似物莫能菌素为半抗原,采用琥珀酸酐法将其改造成莫能菌素-琥珀酰半酯(MON-HS),再用混合酸酐法将其与大分子载体牛血清蛋白(BSA)和卵清蛋白(OVA)偶联,成功制备出了雪卡毒素人工抗原MON-HS-BSA和MON-HS-OVA。以MON-HS-BSA为免疫抗原免疫Balb/c小鼠,以MON-HS-OVA为包被抗原,用间接竞争酶联免疫吸附法(Ci-ELISA)检测到小鼠血清中产生了雪卡毒素的抗体,说明已成功合成雪卡毒素人工抗原,该抗原可用于制备雪卡毒素单克隆抗体。

  12. Synthesis of the EF-ring of ciguatoxin 3C based on the [2,3]-Wittig rearrangement and ring-closing olefin metathesis.

    Science.gov (United States)

    Goto, Akiyoshi; Fujiwara, Kenshu; Kawai, Ayako; Kawai, Hidetoshi; Suzuki, Takanori

    2007-12-20

    The EF-ring segment of ciguatoxin 3C, a causative toxin of ciguatera fish poisoning, was synthesized in three major steps: 1,4-addition for the C20O-C27 bond connection, chirality transferring anti selective [2,3]-Wittig rearrangement for the construction of the anti-2-hydroxyalkyl ether part, and ring-closing olefin metathesis for the F-ring formation.

  13. Update on methodologies available for ciguatoxin determination: perspectives to confront the onset of ciguatera fish poisoning in Europe.

    Science.gov (United States)

    Caillaud, Amandine; de la Iglesia, Pablo; Darius, H Taiana; Pauillac, Serge; Aligizaki, Katerina; Fraga, Santiago; Chinain, Mireille; Diogène, Jorge

    2010-06-14

    Ciguatera fish poisoning (CFP) occurs mainly when humans ingest finfish contaminated with ciguatoxins (CTXs). The complexity and variability of such toxins have made it difficult to develop reliable methods to routinely monitor CFP with specificity and sensitivity. This review aims to describe the methodologies available for CTX detection, including those based on the toxicological, biochemical, chemical, and pharmaceutical properties of CTXs. Selecting any of these methodological approaches for routine monitoring of ciguatera may be dependent upon the applicability of the method. However, identifying a reference validation method for CTXs is a critical and urgent issue, and is dependent upon the availability of certified CTX standards and the coordinated action of laboratories. Reports of CFP cases in European hospitals have been described in several countries, and are mostly due to travel to CFP endemic areas. Additionally, the recent detection of the CTX-producing tropical genus Gambierdiscus in the eastern Atlantic Ocean of the northern hemisphere and in the Mediterranean Sea, as well as the confirmation of CFP in the Canary Islands and possibly in Madeira, constitute other reasons to study the onset of CFP in Europe [1]. The question of the possible contribution of climate change to the distribution of toxin-producing microalgae and ciguateric fish is raised. The impact of ciguatera onset on European Union (EU) policies will be discussed with respect to EU regulations on marine toxins in seafood. Critical analysis and availability of methodologies for CTX determination is required for a rapid response to suspected CFP cases and to conduct sound CFP risk analysis.

  14. Update on Methodologies Available for Ciguatoxin Determination: Perspectives to Confront the Onset of Ciguatera Fish Poisoning in Europe

    Directory of Open Access Journals (Sweden)

    Amandine Caillaud

    2010-06-01

    Full Text Available Ciguatera fish poisoning (CFP occurs mainly when humans ingest finfish contaminated with ciguatoxins (CTXs. The complexity and variability of such toxins have made it difficult to develop reliable methods to routinely monitor CFP with specificity and sensitivity. This review aims to describe the methodologies available for CTX detection, including those based on the toxicological, biochemical, chemical, and pharmaceutical properties of CTXs. Selecting any of these methodological approaches for routine monitoring of ciguatera may be dependent upon the applicability of the method. However, identifying a reference validation method for CTXs is a critical and urgent issue, and is dependent upon the availability of certified CTX standards and the coordinated action of laboratories. Reports of CFP cases in European hospitals have been described in several countries, and are mostly due to travel to CFP endemic areas. Additionally, the recent detection of the CTX-producing tropical genus Gambierdiscus in the eastern Atlantic Ocean of the northern hemisphere and in the Mediterranean Sea, as well as the confirmation of CFP in the Canary Islands and possibly in Madeira, constitute other reasons to study the onset of CFP in Europe [1]. The question of the possible contribution of climate change to the distribution of toxin-producing microalgae and ciguateric fish is raised. The impact of ciguatera onset on European Union (EU policies will be discussed with respect to EU regulations on marine toxins in seafood. Critical analysis and availability of methodologies for CTX determination is required for a rapid response to suspected CFP cases and to conduct sound CFP risk analysis.

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

    Science.gov (United States)

    Kumar-Roiné, Shilpa; Matsui, Mariko; Chinain, Mireille; Laurent, Dominique; Pauillac, Serge

    2008-08-01

    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.

  16. An updated ciguatoxin extraction method and silica cleanup for use with HPLC-MS/MS for the analysis of P-CTX-1, PCTX-2 and P-CTX-3.

    Science.gov (United States)

    Meyer, Lauren; Carter, Steve; Capper, Angela

    2015-12-15

    Ciguatera fish poisoning is a debilitating human neuro-intoxication caused by consumption of tropical marine organisms, contaminated with bioaccumulated ciguatoxins (CTXs). The growing number of cases coupled with the high toxicity of CTXs makes their reliable detection and quantification of paramount importance. Three commonly occurring ciguatoxins, P-CTX-1, 2 and 3 from five different ciguatoxic Spanish mackerel (Scomberomorus commerson), were used to assess the effectiveness of different extraction techniques: homogenization (high powered blending vs. ultrasonication); C-18 column sizes (500 mg vs. 900 mg); and a novel HILIC SPE cleanup. Despite minor differences, blending and sonication proved equally effective. Larger 900 mg columns offered a greater extraction efficiency, increasing detected P-CTX-1 by 37% (P Silica cleanup extraction efficiencies were also compared between the highly effective and validated ciguatoxin rapid extraction method (CREM) and current best practice extraction method employed by Queensland Health (QH). Overall, the QH protocol proved more effective, especially when paired with the newly adapted cleanup, as this increased the amount of extracted P-CTX-1 by 46% (P extracting P-CTX-1, -2, -3. Specifically P-CTX-1, the primary ciguatoxin congener of concern due to its extremely high potency and an ability to cause CFP at 0.1 μg/kg following consumption of carnivorous fish flesh. Despite being more time intensive (an additional 85 min per batch of 12 samples), this will be especially effective for assessing lower toxin burdens, which may be near the limit of detection.

  17. Role of Modular Polyketide Synthases in the Production of Polyether Ladder Compounds in Ciguatoxin-producing Gambierdiscus polynesiensis and G.excentricus (Dinophyceae).

    Science.gov (United States)

    Kohli, Gurjeet S; Campbell, Katrina; John, Uwe; Smith, Kirsty F; Fraga, Santiago; Rhodes, Lesley L; Murray, Shauna A

    2017-02-17

    Gambierdiscus, a benthic dinoflagellate, produces ciguatoxins that cause the human illness Ciguatera. Ciguatoxins are polyether ladder compounds that have a polyketide origin, indicating that polyketide synthases (PKS) are involved in their production. We sequenced transcriptomes of G. excentricus and G. polynesiensis and found 264 contigs encoding single domain ketoacyl synthases (KS; G. excentricus: 106, G. polynesiensis: 143) and ketoreductases (KR; G. excentricus: 7, G. polynesiensis: 8) with sequence similarity to type I PKSs, as reported in other dinoflagellates. Additionally, 24 contigs (G. excentricus: 3, G. polynesiensis: 21) encoding multiple PKS domains (forming typical type I PKSs modules) were found. The proposed structure produced by one of these megasynthases resembles a partial carbon backbone of a polyether ladder compound. Seventeen contigs encoding single domain KS, KR, s-malonyltransacylase, dehydratase and enoyl-reductase with sequence similarity to type II fatty acid synthases (FAS) in plants were found. Type I PKS and type II FAS genes were distinguished based on the arrangement of domains on the contigs and their sequence similarity and phylogenetic clustering with known PKS/FAS genes in other organisms. This differentiation of PKS and FAS pathways in Gambierdiscus is important, as it will facilitate approaches to investigating toxin biosynthesis pathways in dinoflagellates. This article is protected by copyright. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Ryan James C

    2010-08-01

    Full Text Available Abstract Background 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. Results 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 Conclusions Many of the genes differentially expressed in this study, in parallel with the hypothermia, figure prominently in protection against

  19. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury

    Science.gov (United States)

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-01-01

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury. PMID:27229176

  20. Research Advance on Detection and Analysis of Ciguatoxin%西加毒素检测分析研究新进展

    Institute of Scientific and Technical Information of China (English)

    周秀锦; 李孝军; 何明; 周向阳; 邵宏宏; 颜建波

    2013-01-01

    Ciguatoxins(CTXs) may be an acquired coral fish toxin. CTXs are a family of lipidsoluble cyclic polyethers which have strong and irreversible choline esterase inhibition. Several approaches were developed in the past decades to address this issue because of some drawbacks are not the convenient and accurate detection method for CTXs. To provide references for detection and prevention of ciguatera fish poisoning, development of aquatic products industry, protection public health, the current detection methods of CTXs were reviewed.%西加毒素是一种属于获得性毒素的珊瑚鱼毒素,为脂溶性多聚醚类化合物,有强烈的和不可逆的胆碱酶抑制毒性.从发现西加毒素至今,有不同的检测方法提出,但都不能满足适应市场的需求.主要对西加毒素现有的检测分析方法进行了综述,将有助于多种检测方法更好地提高与完善,对于西加毒素中毒防治、水产业的顺利发展以及公众的健康都具有重要意义.

  1. Ciguatoxin reduces regenerative capacity of axotomized peripheral neurons and delays functional recovery in pre-exposed mice after peripheral nerve injury.

    Science.gov (United States)

    Au, Ngan Pan Bennett; Kumar, Gajendra; Asthana, Pallavi; Tin, Chung; Mak, Yim Ling; Chan, Leo Lai; Lam, Paul Kwan Sing; Ma, Chi Him Eddie

    2016-05-27

    Ciguatera fish poisoning (CFP) results from consumption of tropical reef fish containing ciguatoxins (CTXs). Pacific (P)-CTX-1 is among the most potent known CTXs and the predominant source of CFP in the endemic region responsible for the majority of neurological symptoms in patients. Chronic and persistent neurological symptoms occur in some CFP patients, which often result in incomplete functional recovery for years. However, the direct effects of exposure to CTXs remain largely unknown. In present study, we exposed mice to CTX purified from ciguatera fish sourced from the Pacific region. P-CTX-1 was detected in peripheral nerves within hours and persisted for two months after exposure. P-CTX-1 inhibited axonal regrowth from axotomized peripheral neurons in culture. P-CTX-1 exposure reduced motor function in mice within the first two weeks of exposure before returning to baseline levels. These pre-exposed animals exhibited delayed sensory and motor functional recovery, and irreversible motor deficits after peripheral nerve injury in which formation of functional synapses was impaired. These findings are consistent with reduced muscle function, as assessed by electromyography recordings. Our study provides strong evidence that the persistence of P-CTX-1 in peripheral nerves reduces the intrinsic growth capacity of peripheral neurons, resulting in delayed functional recovery after injury.

  2. 钠离子荧光探针用于检测雪卡毒素的细胞毒性%A cell-based detection of ciguatoxin using sodium fluorescence probe

    Institute of Scientific and Technical Information of China (English)

    袁建辉; 杨慧; 唐焕文; 黄薇; 徐新云; 刘建军; 柯跃斌; 程锦泉; 庄志雄

    2011-01-01

    Objective To establish a cell-based detection method of ciguatoxin using fluorescence assay. Methods Mouse neuroblastoma N-2A cells were exposed to ouabain and veratridine and different concentrations of standard ciguatoxin samples (P-CTX-1) to establish the curvilinear relationship between the toxin dosage and fluorescence intensity using the sodium fluorescence probe CoroNa? Green. The toxicity curvilinear relationship was also generated between the toxin dosage and cell survival using CCK-8 method. Based on these standard curves, the presence of ciguatoxin was detected in 33 samples of deep-sea coral fish. Results A correlation was found between the detection results of cell-based fluorescence assay and cytotoxicity assay, whose detection limit reached 10"13 g/ml and 10-12 g/ml, respectively. The cell-based fluorescent assay sensitivity showed a higher sensitivity than cytotoxicity assay with a 2-4 h reduction of the detection time. Conclusions The cell-based fluorescent assay can quickly and sensitively detect ciguatoxin and may serve as a good option for preliminary screening of the toxin.%目的 研究和建立以细胞为基础的结合钠离子荧光探针检测雪卡毒素的方法,为快速、敏感检测雪卡毒素提供科学的实验依据.方法 采用雪卡毒素标准品(p-CTX-1)结合乌苯苷和黎芦定处理小鼠脑神经瘤细胞(N-2A),用钠离子荧光探针(CoroNaTM Green)标记细胞,利用多功能酶标仪检测荧光强度,建立雪卡毒素浓度与荧光强度的标准曲线关系式;同时,采用CCK-8法和酶标仪检测毒素处理组细胞的存活率,建立细胞毒性实验的标准曲线关系式;分析比较两种方法的灵敏度.以两种方法分别对采集的33份深海珊瑚鱼样品进行毒素检测,对检测结果作分析比较.结果 以细胞为基础的荧光检测法检测样品中毒素的检出限为10-13g/ml,而细胞毒性试验检测法检测样品中毒素的检出限为10-12g/ml,其结果具有一定的

  3. Comparative study of two methods for detection of ciguatoxins%雪卡毒素两种检测方法的比较研究

    Institute of Scientific and Technical Information of China (English)

    蔡朝民; 袁建辉; 谢猛; 赵昆山; 江天久; 刘建军; 黄薇; 庄志雄

    2009-01-01

    Objective To establish a methods of cytotoxicity assay and mouse bioaasay. Methods The toxicity curvilinear relationship between the toxin dosage and cytoactive was established by the use of toxin standard samples (P-CTX-1)in different concentration and conjugated Ouabain and Vemtridine. At the same time,the detection standard of mouse bioassay was established through detecting the ciguatera toxin medial lethal dose LD50 about Kunming mouse and the relation equation between toxin dosage and death time of Kunming mouse,in addition,the detection results of the two methods were explored by detecting toxin extractive from the 32 portions fish samples in different months. Results There was certain dependability between the detection results of eytotoxieity assay and the detection results of mouse bioassay, however,the sensitivity of cytotoxicity assay was better than mouse bioassay. Conclusion The detection methods of cytotoxicity assay is applicable to screen considerable samples preliminarily, nevertheless, mouse bioassay could be a kind of important reference method for detection of ciguatoxins.%目的 建立雪卡毒素的细胞毒性试验检测和小鼠生物法检测方法,对比评价两种方法的优缺点.方法 利用不同浓度的雪卡毒素标准品(P-CTX-1)结合乌苯苷和黎芦定处理小鼠神经母细胞瘤细胞(N-2a),研究和建立毒素剂量与细胞活性的毒性曲线关系式.同时,通过测定昆明系小白鼠的雪卡毒素半数致死剂量LD50和毒素剂量与小鼠死亡时间的关系方程式,建立小鼠生物法检测标准,再分别以两种方法对32份不同月份采集的鱼样品的毒素提取物进行检测,对两种方法检测结果做分析比较. 结果细胞毒性试验法检测结果与小鼠生物法检测结果具有一定的相关性,但细胞毒性试验法检测雪卡毒素的检测灵敏度远高于小鼠生物法.结论 细胞毒性试验检测法适用于大量样品的初步筛选方法,而小鼠生物

  4. Towards the standardisation of the neuroblastoma (neuro-2a) cell-based assay for ciguatoxin-like toxicity detection in fish: application to fish caught in the Canary Islands.

    Science.gov (United States)

    Caillaud, A; Eixarch, H; de la Iglesia, P; Rodriguez, M; Dominguez, L; Andree, K B; Diogène, J

    2012-01-01

    The ouabain/veratridine-dependent neuroblastoma (neuro-2a) cell-based assay (CBA) was applied for the determination of the presence of ciguatoxin (CTX)-like compounds in ciguatera-suspected fish samples caught in the Canary Islands. In order to avoid matrix interferences the maximal concentration of wet weight fish tissue exposed to the neuro-2a cells was set at 20 mg tissue equivalent (TE) ml(-1) according to the sample preparation procedure applied. In the present study, the limit of quantification (LOQ) of CTX1B equivalents in fish extract was set at the limit of detection (LOD), being defined as the concentration of CTX1B equivalents inhibiting 20% cell viability (IC(20)). The LOQ was estimated as 0.0096 ng CTX1B eq.g TE(-1) with 23-31% variability between experiments. These values were deemed sufficient even though quantification given at the IC(50) (the concentration of CTX1B equivalents inhibiting 50% cell viability) is more accurate with a variability of 17-19% between experiments. Among the 13 fish samples tested, four fish samples were toxic to the neuro-2a cells with estimations of the content in CTX1B g(-1) of TE ranging from 0.058 (± 0.012) to 6.23 (± 0.713) ng CTX1B eq.g TE(-1). The high sensitivity and specificity of the assay for CTX1B confirmed its suitability as a screening tool of CTX-like compounds in fish extracts at levels that may cause ciguatera fish poisoning. Species identification of fish samples by DNA sequence analysis was conducted in order to confirm tentatively the identity of ciguatera risk species and it revealed some evidence of inadvertent misidentification. Results presented in this study are a contribution to the standardisation of the neuro-2a CBA and to the risk analysis for ciguatera in the Canary Islands.

  5. High Performance Liquid Chromatography Coupled with Electrospray Tandem Mass Spectrometry for Analysis of Pacific Ciguatoxin in Fishes%高效液相色谱-电喷雾串联质谱法测定鱼体中雪卡毒素

    Institute of Scientific and Technical Information of China (English)

    刘红河; 刘桂华; 杨俊; 陈裕华; 朱舟

    2009-01-01

    建立了高效液相色谱-电喷雾串联质谱法测定鱼体中雪卡毒素P-CTX1含量的方法.鱼类样品经丙酮提取后,用冷冻脱脂,经PSA固相萃取柱净化后,C_(18)色谱柱分离,采用电喷雾串联四极杆质谱进行检测.结果表明,雪卡毒素在0.5~20 μg/L范围时,线性关系良好(r=0.9998).P-CTX1在添加浓度为1.0~20.0 ng/kg范围内的平均回收率为82.3%~87.2%,相对标准偏差小于7.8%,方法的定量检出限为0.1 μg/L.%A sensitive method was developed for the determination of pacific ciguatoxin (P-CTX1) residue in fishes by high performance liquid chromatography coupled with electrospray tandem mass spectrometry ( HPLC-MS/MS). Homogenized samples of fish was extracted with acetone,degreased by freezing under -20℃ and filtered with filter paper. Then the supernatant was cleaned up with PSA column. Identification was achieved by electrospray ionization (ESI) in positive mode using multiple reaction monitoring. The calibration curve of P-CTX1 showed good linearity in the range of 0.5 -20μg/L with correlation coefficient of 0.9998. The limit of quantitation (LOQ) was 0. 1 mg/L( S/N = 10). The recoveries of P-CTX1 were between 82. 3% and 87. 2% (n =7) at spiked levels of 1.0 -20.0 ng/kg. The relative standard derivations( RSD) of the method were less than 7.8%.

  6. Rapid determination of three Pacific ciguatoxins in muscle of moral eel by high performance liquid chromatography-tandem mass spectrometry%高效液相色谱-串联质谱法快速测定海鳗鱼肉中3种太平洋雪卡毒素

    Institute of Scientific and Technical Information of China (English)

    麦艳玲; 林珊珊; 肖陈贵; 岳振峰; 吴佳俊; 康海宁; 林群声; 陈荔

    2014-01-01

    目的:建立了一种平行振荡方法萃取海鳗鱼肉中的3种太平洋雪卡毒素(P-CTX-1、P-CTX-2、P-CTX-3),并采用高效液相色谱-电喷雾串联质谱法同时测定P-CTX-1、P-CTX-2、P-CTX-3残留量的分析方法。方法海鳗等样品经甲醇并采用平行振荡方法提取, C18固相萃取柱净化后,采用高效液相色谱-电喷雾串联质谱分析测定。结果以基质标准曲线外标法定量,线性范围为0.01∼50.0 ng/g,相关系数均大于0.999(r≥0.999, n=3), P-CTX-1、P-CTX-2、P-CTX-3的定量限分别为(LOQs,S/N=10)0.009、0.019、0.017 ng/g。以0.05、0.10、0.50 ng/g 3个添加浓度水平进行方法验证,回收率分别为72.9~81.0%、63.0~77.9%、46.3~69.5%,相对标准偏差分别为2.3~2.7%、2.1~12.2%、6.1~15.3%。结论该方法简便快速、灵敏度高,适用于鱼肉中同时快速检测3种太平洋雪卡毒素。%Objective A parallel shaking method was developed to extract three Pacific ciguatoxins (P-CTX-1, P-CTX-2, P-CTX-3) in muscle samples of moray eel and a rapid simultaneous quantification me-thod was optimized to quantify P-CTXs in fish muscle using high performance liquid chromatography coupled with electrospray-tandem mass spectrometry (HPLC-MS/MS).MethodsMuscle samples of moray eel were extracted in methanol using parallel shaker. Crude extract was then cleaned-up by C18 solid-phase extraction (SPE) cartridges. High performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was employed to identify and quantify P-CTXs.ResultsThe quantification of P-CTX-1, P-CTX-2 and P-CTX-3 were performed using matrix-matched calibrations with correlation coefficients above 0.999 (r≥0.999,n=3). The linearity of the calibration curves ranged from 0.01~50.0 ng/g. The limits of quantification (LOQs,S/N=10) of P-CTX-1, P-CTX-2 and P-CTX-3 were 0.009, 0.019, and 0.017 ng/g. Method validation was carried out by spiking three levels of P-CTXs (i.e. 0.05, 0.10, and 0.50 ng/g) to fish muscle. The

  7. Cardiovascular complications in ciguatera fish poisoning: A wake-up call

    Directory of Open Access Journals (Sweden)

    Subramanian Senthilkumaran

    2011-01-01

    Full Text Available Ciguatera fish poisoning occurs with ingestion of fish containing ciguatoxin. It causes a clinical syndrome that comprises classic gastrointestinal, neurological and cardiovascular symptoms. Ciguatoxin is a sodium channel agonist with cholinergic and adrenergic activity. Although cardiovascular symptoms are rare with ciguatoxin, we report two cases with bradycardia and hypotension. Fatality and long-term sequelae are not uncommon with ciguatoxin poisoning and educating the general population is essential.

  8. Use of monoclonal antibodies as an effective strategy for treatment of ciguatera poisoning.

    Science.gov (United States)

    Inoue, Masayuki; Lee, Nayoung; Tsumuraya, Takeshi; Fujii, Ikuo; Hirama, Masahiro

    2009-06-01

    Ciguatera is a global food poisoning caused by the consumption of fish that have accumulated sodium channel activator toxins, ciguatoxins. At present, most diagnosed cases of ciguatera are treated with symptomatic and supportive remedies, and no specific therapy has been devised. Here we report that ciguatoxin CTX3C can be effectively neutralized in vitro and in vivo by simultaneous use of two anti-ciguatoxin monoclonal antibodies, providing the first rational approach toward directly preventing and treating ciguatera.

  9. Molecular Docking and Molecular Dynamics Simulation Studies of Toxicity Mechanism of Ciguatoxin%雪卡毒素毒性机理的分子对接及分子动力学研究

    Institute of Scientific and Technical Information of China (English)

    郑杰; 赵斌; 闫鸿鹏; 张焜; 张大鹏; 赵肃清

    2011-01-01

    采用分子对接和分子动力学方法,研究了雪卡毒素与其毒性作用靶点之一钠通道的结合模式,并与钠通道阻滞剂奎尼丁比较.研究结果表明,雪卡毒素、奎尼丁与钠通道作用方式有所不同.分子动力学模拟表明,对接受体-配体复合物体系在2.5 ns的模拟过程中稳定.奎尼丁在钠通道中央与GLU1784,THR1858各形成1个稳定氢键,吡啶环与PHE1791有疏水相互作用.雪卡毒素在钠通道外侧与SER1782,GLU1784,LEU1786以及GLU1788各形成1个持续存在的氢键,从而激活钠通道产生毒性作用.%Binding modes between CTX(Ciguatoxin) and sodium channel,which is one of the targets about CTX toxic effects,were simulated through molecular docking and dynamics method,compared with Quinidine.The docking results indicated that CTX and Quinidine shared different binding modes to sodium channel.The ligand-receptor complexes obtained by molecular docking are stable during 2.5 ns molecular dynamics simulation.Quinidine is tightly held to sodium channel centeral residues of GLU1784 and THR1858 with one hydrogen bond respectively.Its pyridine ring has hydrophobic interactions with residue of PHE1791,which produces the effect of sodium channel block.The binding site of CTX is far away from sodium channel center,one stable hydrogen bond interaction has been formed with residues of SER1782,GLU1784,LEU1786 and GLU1788 respectively.It may promote sodium channel opening and activate so-dium channel,and produce its toxic effects.

  10. The Effects of Microbes on Growth of Gambierdiscus spp.and Ciguatoxin Distribution%微生物对纲比甲藻生长以及区域雪卡毒性分布的影响

    Institute of Scientific and Technical Information of China (English)

    王博; 姚蜜蜜; 晋慧; 赵丽红; 相建海; 蔡中华

    2015-01-01

    目的:雪卡鱼毒中毒(Ciguatera fish poisoning)严重危害人类健康,同时带来巨大经济损失.雪卡毒素起源于雪卡鱼食用了有毒的底栖生物纲比甲藻(Gambierdiscus spp.).由于全球雪卡毒素中毒的分布呈现时空变化性,在小范围内又存在区域特异性分布的特征,科学家很难作出解释.一直以来对影响纲比甲藻生长的生物因素较环境因子的研究而言非常有限,本文从藻菌关系的角度出发,研究重要微生物对纲比甲藻生长的影响,进而解释雪卡毒性区域特异性分布的现象.方法:采用宏基因组多样性分析和相关性分析找出毒性相关微生物,结合生物被膜相关微生物筛选结果,选定重要细菌对一株纲比甲藻进行生长刺激试验,通过藻类计数方法研究微生物对纲比甲藻生长的影响.结果:不同毒性区域存在特异性的微生物群落组成,部分微生物与雪卡毒性分布具有相关性.四株刺激菌中三株显著提升了纲比甲藻的生长能力,一株对纲比甲藻具有抑制作用.结论:重要微生物可能通过影响纲比甲藻在食物链中数量的积累,导致雪卡毒性区域特异性分布.对生物因素的研究是今后雪卡毒素研究领域的新方向,具有重要的借鉴意义和应用价值.

  11. [Toxin profiles in fish implicated in ciguatera fish poisoning in Amami and Kakeroma Islands, Kagoshima Prefecture, Japan].

    Science.gov (United States)

    Yogi, Kentaro; Oshiro, Naomasa; Matsuda, Seiko; Sakugawa, Satsuki; Matsuo, Toshiaki; Yasumoto, Takeshi

    2013-01-01

    Ciguatoxins (CTXs) responsible for ciguatera fish poisoning (CFP) in Amami Islands, Kagoshima, Japan in 2008 were determined by LC-MS/MS analysis. Ciguatoxin-1B (CTX1B), 54-deoxyCTX1B, and 52-epi-54-deoxyCTX1B were detected in Variola louti and Lutjanus monostigma. The toxin profile distinctly differed from that of a CFP-related fish from Miyazaki, which mainly contained ciguatoxin-3C type toxins. Toxin profiles were species-specific, as observed in fish from Okinawa. The LC-MS/MS and mouse bioassay (MBA) methods produced comparable data, though 54-deoxyCTX1B was not taken into consideration owing to the lack of toxicity data. To improve assessment, toxicity data for this compound are needed. A reef fish caught on the same occasion and judged nontoxic by MBA (<0.025 MU/g) was found to contain low levels of CTX, indicating a potential risk for CFP.

  12. Ciguatera: a public health perspective.

    Science.gov (United States)

    Dickey, Robert W; Plakas, Steven M

    2010-08-15

    Ciguatera fish poisoning is a seafood-borne illness caused by consumption of fish that have accumulated lipid-soluble ciguatoxins. In the United States, ciguatera is responsible for the highest reported incidence of food-borne illness outbreaks attributed to finfish, and it is reported to hold this distinction globally. Ciguatoxins traverse the marine food web from primary producers, Gambierdiscus spp., to commonly consumed fish in tropical and subtropical regions of the world. Ciguatoxins comprise 12 known congeners among Caribbean and tropical Atlantic fish and 29 reported congeners among Pacific fish. Expanding trade in fisheries from ciguatera-endemic regions contributes to wider distribution and increasing frequency of disease among seafood consumers in non-endemic regions. Ciguatoxins produce a complex array of gastrointestinal, neurological and cardiological symptoms. Treatment options are very limited and supportive in nature. Information derived from the study of ciguatera outbreaks has improved clinical recognition, confirmation, and timely treatment. Such studies are equally important for the differentiation of ciguatoxin profiles in fish from one region to the next, the determination of toxicity thresholds in humans, and the formulation of safety limits. Analytical information from case and outbreak investigations was used to derive Pacific and Caribbean ciguatoxin threshold contamination rates for adverse effects in seafood consumers. To these threshold estimates 10-fold safety factors were applied to address individual human risk factors; uncertainty in the amount of fish consumed; and analytical accuracy. The studies may serve as the basis for industry and consumer advisory levels of 0.10ppb C-CTX-1 equivalent toxicity in fish from the tropical Atlantic, Gulf of Mexico, Caribbean, and 0.01ppb P-CTX-1 equivalent toxicity in fish from Pacific regions.

  13. Ciguatera fish poisoning: a review

    NARCIS (Netherlands)

    Fouw JC de; Egmond HP van; Speijers GJA; CSR

    2001-01-01

    This review on ciguatera fish poisoning contains information on the ciguatera intoxication syndrome and the provoking ciguatoxins (CTXs) and gambiertoxin-4b (GTX-4B), of which CTX-1 is a major component at the end of food chain (the carnivore fish). Data on chemical structures and detection methods

  14. 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.

    Science.gov (United States)

    O'Toole, Amanda C; Dechraoui Bottein, Marie-Yasmine; Danylchuk, Andy J; Ramsdell, John S; Cooke, Steven J

    2012-06-15

    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 211.74pg 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 approach with biotelemetry and biologging techniques that enable the study of fish distribution and movement. To demonstrate the potential for linking ciguatoxin occurrence with barracuda spatial ecology, we also present a proof-of-concept case study where 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 44km(2). 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 from blood provide future opportunities to understand the mechanistic relationship between toxins and the spatial ecology of a broad range of marine fish species.

  15. Ionic mechanisms of spinal neuronal cold hypersensitivity in ciguatera.

    Science.gov (United States)

    Patel, Ryan; Brice, Nicola L; Lewis, Richard J; Dickenson, Anthony H

    2015-12-01

    Cold hypersensitivity is evident in a range of neuropathies and can evoke sensations of paradoxical burning cold pain. Ciguatoxin poisoning is known to induce a pain syndrome caused by consumption of contaminated tropical fish that can persist for months and include pruritus and cold allodynia; at present no suitable treatment is available. This study examined, for the first time, the neural substrates and molecular components of Pacific ciguatoxin-2-induced cold hypersensitivity. Electrophysiological recordings of dorsal horn lamina V/VI wide dynamic range neurones were made in non-sentient rats. Subcutaneous injection of 10 nm ciguatoxin-2 into the receptive field increased neuronal responses to innocuous and noxious cooling. In addition, neuronal responses to low-threshold but not noxious punctate mechanical stimuli were also elevated. The resultant cold hypersensitivity was not reversed by 6-({2-[2-fluoro-6-(trifluoromethyl)phenoxy]-2-methylpropyl}carbamoyl)pyridine-3-carboxylic acid, an antagonist of transient receptor potential melastatin 8 (TRPM8). Both mechanical and cold hypersensitivity were completely prevented by co-injection with the Nav 1.8 antagonist A803467, whereas the transient receptor potential ankyrin 1 (TRPA1) antagonist A967079 only prevented hypersensitivity to innocuous cooling and partially prevented hypersensitivity to noxious cooling. In naive rats, neither innocuous nor noxious cold-evoked neuronal responses were inhibited by antagonists of Nav 1.8, TRPA1 or TRPM8 alone. Ciguatoxins may confer cold sensitivity to a subpopulation of cold-insensitive Nav 1.8/TRPA1-positive primary afferents, which could underlie the cold allodynia reported in ciguatera. These data expand the understanding of central spinal cold sensitivity under normal conditions and the role of these ion channels in this translational rat model of ciguatoxin-induced hypersensitivity.

  16. Production of a Purified Marine Neurotoxin and Demonstration of its Binding Affinity to Ion Channel Receptors

    Science.gov (United States)

    1989-06-10

    Saxitoxin Conotoxins 2 Batrachotoxin Persistent activation Veratrum alkaloids Grayanotoxins 3 a- scorpion toxins Inhibit inactivation sea anemone... toxins 4 b- scorpion toxins Shift activation 5 Brevetoxins Shift activation and Ciguatoxin Inhibit J.nactivation Baden 1989 5 The objectives of this study...includes 1) demonstration of dinoflagellate toxin binding to synaptosome ion ch nnels 2) investigation of the effects of maitotoxin on the binding of

  17. Mild ciguatera poisoning: Case reports with neurophysiological evaluations.

    Science.gov (United States)

    Butera, R; Prockop, L D; Buonocore, M; Locatelli, C; Gandini, C; Manzo, L

    2000-10-01

    Ciguatera poisoning causes mainly gastrointestinal and neurological effects of variable severity. However, symptoms of peripheral neuropathy with paresthesias and paradoxical disturbance of thermal sensation are the hallmark. Electrophysiological studies are often normal, except in severe cases. We report four people who developed mild ciguatera poisoning after barracuda ingestion. Electrophysiological studies documented normocalcemic latent tetany. These findings are consistent with ciguatoxin's mechanism of toxicity, which involves inactivation of voltage-gated Na(+) channels and eventually increases nerve membrane excitability.

  18. Normal axonal ion channel function in large peripheral nerve fibers following chronic ciguatera sensitization.

    Science.gov (United States)

    Vucic, Steve; Kiernan, Matthew C

    2008-03-01

    Although the acute clinical effects of ciguatera poisoning, due to ingestion of ciguatoxin, are mediated by activation of transient Na+ channels, the mechanisms underlying ciguatera sensitization remain undefined. Axonal excitability studies were performed by stimulating the median motor and sensory nerves in two patients with ciguatera sensitization. Excitability parameters were all within normal limits, thereby arguing against dysfunction of axonal membrane ion channels in large-diameter fibers in ciguatera sensitization.

  19. Marine Biotoxins: Laboratory Culture and Molecular Structure

    Science.gov (United States)

    1988-10-11

    principally concerned with two toxins that are associated with the human fish intoxication known as ciguatera , ciguatoxin and maitotoxin, both of unknown...mouse anti- Hokama uses rapidly reprodu. bodies, which react to any cing mouse cancer cells that are ciguatera toxin in fish. fused with normal...in a Ciguatera poisoning results computer-controlled incubator from the consumption of certain at the UH riomedical Building. reef fish, including kole

  20. Epidemiology and Clinical Features of Ciguatera Fish Poisoning in Hong Kong

    OpenAIRE

    Thomas Y. K. Chan

    2014-01-01

    In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2) per million people. The groupers have replaced the snappers as the most important cause of ciguatera. Pacific-ciguatoxins (CTX) are most commonly present in reef fish samples implicated in ciguatera outbreaks. In affected subjects, the gastrointestinal symptoms...

  1. Practical route to the left wing of CTX1B and total syntheses of CTX1B and 54-deoxyCTX1B.

    Science.gov (United States)

    Yamashita, Shuji; Takeuchi, Katsutoshi; Koyama, Takuya; Inoue, Masayuki; Hayashi, Yujiro; Hirama, Masahiro

    2015-02-02

    Ciguatoxins, the principal causative agents of ciguatera seafood poisoning, are extremely large polycyclic ethers. We report herein a reliable route for constructing the left wing of CTX1B, which possesses the acid/base/oxidant-sensitive bisallylic ether moiety, by a 6-exo radical cyclization/ring-closing metathesis strategy. This new route enabled us to achieve the second-generation total synthesis of CTX1B and the first synthesis of 54-deoxyCTX1B.

  2. Ciguatoxic Potential of Brown-Marbled Grouper in Relation to Fish Size and Geographical Origin

    OpenAIRE

    Thomas Y. K. Chan

    2015-01-01

    To determine the ciguatoxic potential of brown-marbled grouper (Epinephelus fuscoguttatus) in relation to fish size and geographical origin, this review systematically analyzed: 1) reports of large ciguatera outbreaks and outbreaks with description of the fish size; 2) Pacific ciguatoxin (P-CTX) profiles and levels and mouse bioassay results in fish samples from ciguatera incidents; 3) P-CTX profiles and levels and risk of toxicity in relation to fish size and origin; 4) regulatory measures r...

  3. Ciguatera fish poisoning in the Caribbean islands and Western Atlantic.

    Science.gov (United States)

    Pottier, I; Vernoux, J P; Lewis, R J

    2001-01-01

    Ciguatera fish poisoning (ciguatera), a common poisoning caused by fish ingestion, is reviewed in the Western Atlantic and the Caribbean waters. It is endemic from Florida coasts (northern limit) to Martinique Island (southern limit), with outbreaks occurring from time to time. In the Caribbean, ciguatera causes a polymorphic syndrome with gastrointestinal, cardiovascular, and neurological signs and symptoms. Neurological and muscular dysfunctions can be treated by intravenous injection of D-mannitol. The lipid-soluble toxins involved are ciguatoxins that are likely produced by the dinoflagellate Gambierdiscus toxicus. G. toxicus strains are endemic in the Caribbean Sea and in theWestern Atlantic. Although it is likely that blooms of G. toxicus are ingested by herbivorous fishes, they are not implicated in ciguatera in the Caribbean. Rather, large carnivores (barracudas, jacks, snappers, groupers), consumers of smaller benthic fish, are often involved in ciguatera. Fish toxicity depends on fishing area and depth, fish size and tissues, and climatic disturbances. Ciguatoxins have been isolated and purified from Caribbean fish species. The structure of two epimers, C-CTX-1 and C-CTX-2 from horse-eye jack, comprise 14 trans-fused ether-linked rings and a hemiketal in terminal ring. Caribbean ciguatoxins are mainly detected in the laboratory by chicken, mouse, mosquito, or cell bioassays, and by analytical HPLC/tandem mass spectrometry down to parts per billion (ppb). A ciguatera management plan that integrates epidemiology, treatment, and a simple method of detection is required to ensure the protection of consumers.

  4. Survey of ciguatera at Enewetak and Bikini, Marshall Islands, with notes on the systematics and food habits of ciguatoxic fishes

    Energy Technology Data Exchange (ETDEWEB)

    Randall, J.E.

    1980-04-01

    A total of 551 specimens of 48 species of potentially ciguatoxic fishes from Enewetak and 256 specimens of 23 species from Bikini, Marshall Islands, were tested for ciguatoxin by feeding liver or liver and viscera from these fishes to mongooses at 10% body weight (except for sharks, when only muscle tissue was used). The fishes are representatives of the following families: Orectolobidae, Carcharhinidae, Dasyatidae, Muraenidae, Holocentridae, Sphyraenidae, Mugilidae, Serranidae, Lutjanidae, Lethrinidae, Carangidae, Scombridae, Labridae, Scaridae, Acanthuridae, and Balistidae. The species selected were all ones for which toxicity can be expected, including the worst offenders from reports of ciguatera throughout Oceania; only moderate to large-sized adults were tested. In all, 37.3% of the fishes from Enewetak and 19.7% from Bikini gave a positive reaction for ciguatoxin. Because liver and other viscera are more toxic than muscle, the percentage of positive reactions at the level which might cause illness in humans eating only the flesh of these fishes collectively would drop to 16.2 for Enewetak and 1.4 for Bikini. This level of toxicity is not regarded as high for Pacific islands, in general. Because ciguatoxin is acquired through feeding, the food habits of these fishes were investigated. Most of the highly toxic species, including seven of the eight causing severe illness or death in the test animals (Lycodontis javanicus, Cephalopholis argus, Epinephelus hoedtii, E. microdon, Plectropomus leopardus, Aprion virescens, and Lutjanus bohar) are primarily piscivorous.

  5. Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary Islands (Spain).

    Science.gov (United States)

    Boada, Luis D; Zumbado, Manuel; Luzardo, Octavio P; Almeida-González, Maira; Plakas, Steven M; Granade, Hudson R; Abraham, Ann; Jester, Edward L E; Dickey, Robert W

    2010-12-01

    Ciguatera fish poisoning (CFP) is endemic in certain tropical and subtropical regions of the world. CFP had not been described on the West Africa Coast until a 2004 outbreak in the Canary Islands. In 2008-2009, two additional outbreaks of ciguatera occurred. Individuals afflicted had consumed lesser amberjack (Seriola rivoliana) captured from nearby waters. Caribbean ciguatoxin-1 (C-CTX-1) was confirmed in fish samples by LC-MS/MS. Ciguatoxic fish in this region may pose a new health risk for the seafood consumer.

  6. 2005年厦门市三起雪卡毒素中毒情况分析%Study of three ciguatera fish poisoning cases in Xiamen city,in 2005

    Institute of Scientific and Technical Information of China (English)

    骆和东; 白艳艳; 周娜

    2011-01-01

    Objective To find out the reason of three eiguatem fish poisoning cases in Xiaman in 2005 and identify the fish species.Methods The grouper implicated in food poisoning and seven other coral reef fishes collected from market were tested by mice bioassay and ciguatoxin-test kit.The mtDNA was extracted from toxic grouper meat,and Cty b gene segment was amplified and the PCR products were sequenced.The sequences were compared with those in the GenBank.Results The result turned out to be positive by the ciguatoxin-test kit,while the toxicity of the toxic grouper implicated in food poisoning was 0.11 mouse unit(MU)/g by mice bioassay.A 475 bp segments of Cty b gene was amplified by PCR and the sequence was 99% homologous with Epinephelus fuscoguttatus(GenBank:AY950695).No ciguatoxin in six grouper species collected from market was detected.Conclusion All three food poisoning cases were caused by consumption of ciguatoxin-carrying groupers.%目的 分析引发2005年厦门3起雪卡毒素中毒的原因及引发中毒的鱼种.方法 采集3起中毒案例中剩余的棕点石斑鱼及市场上其他深海鱼共7份,采用小鼠生物法、雪卡毒素免疫膜试剂盒测定雪卡毒素,同时提取中毒鱼肉组织中的mtDNA,采用PCR技术扩增细胞色素6(Cry b)部分序列片段并直接测序,将结果与CenBank数据库比对.结果 引发中毒的鱼肉中雪卡毒素检测呈阳性,小鼠生物实验毒性为0.11小鼠单位(MU)/g,提取的mtDNA扩增出475 bp大小的Cty b基因片段,与棕点石斑鱼(登录号 AY950695)的Cry b基因相似性达99%.其余6份样品均未检出雪卡毒素.结论 这3起中毒事件均是由于食用了含有雪卡毒素的棕点石斑鱼而引发的食物中毒.

  7. Ciguatera: Australian perspectives on a global problem.

    Science.gov (United States)

    Lewis, Richard J

    2006-12-01

    Ciguatera is a global disease caused by the consumption of certain warm-water fish that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. Symptoms of ciguatera arising from the consumption of ciguateric fish include a range of gastrointestinal, neurological and cardiovascular disturbances. This review examines progress in our understanding of ciguatera from an Australian perspective, especially the laboratory-based research into the problem that was initiated by the late "Bob" Endean at the University of Queensland.

  8. Large Outbreaks of Ciguatera after Consumption of Brown Marbled Grouper

    Directory of Open Access Journals (Sweden)

    Thomas Y. K. Chan

    2014-07-01

    Full Text Available Brown marbled grouper (Epinephelus fuscoguttatus is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100–200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1–2 days. Some neurological symptoms (e.g., paresthesia of four limbs could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use and repeated ciguatoxin exposures will result in more severe and chronic illness.

  9. [Evaluation of Antilles fish ciguatoxicity by mouse and chick bioassays].

    Science.gov (United States)

    Pottier, I; Vernoux, J P

    2003-03-01

    Ciguatera is a common seafood poisoning in Western Atlantic and French West Indies. Ciguatera fish poisoning in the Caribbean is a public health problem. A toxicological study was carried out on 178 Caribbean fish specimens (26 species) captured off Guadeloupe and Saint Barthelemy between 1993 and 1999. The mouse bioassay and the chick feeding test were used to control fish edibility. Ciguatoxins presence was assumed when symptomatology was typical of ciguatera in mouse and chick. Fishes were classified in three groups: non toxic fish (edible), low toxic fish (not edible) and toxic fish (not edible). 75% of fishes were non toxic. Toxic fish specimens belonged to four families of high trophic level carnivores: Carangidae, Lutjanidae, Serranidae et Sphyraenidae. Percentages of toxic fishes to humans reached 55% for Caranx latus and 33% for Caranx bartholomaei and Caranx lugubris. Only a significant correlation between weight and toxicity was only found for C. latus and snappers. Small carnivorous groupers (Serranidae) were also toxic. Atoxic fish species were (a) pelagic fish (Coryphaena hippurus, Auxis thazard and Euthynnus pelamis), (b) invertebrates feeders (Malacanthus plumieri, Balistes vetula), (c) small high-risk fish or (d) fish of edible benthic fish families. Liver of four fishes (Mycteroperca venenosa, Caranx bartholomaei, Seriola rivoliana, Gymnothorax funebris) contained ciguatoxins at a significant level although their flesh was safe. This study confirms the usefulness of mouse and chick bioassays for sanitary control of fish.

  10. Use of Surveillance Systems in Detection of a Ciguatera Fish Poisoning Outbreak - Orange County, Florida, 2014.

    Science.gov (United States)

    Klekamp, Benjamin G; Bodager, Dean; Matthews, Sarah D

    2015-10-16

    What is already known on this topic? Ciguatera fish poisoning (CFP), caused by the ingestion of predatory reef-dwelling fish harboring ciguatoxins is one of the most commonly reported fish-associated marine intoxications. Ciguatoxin retains toxicity regardless of freezing or cooking. Prompt treatment can reduce debilitating neurologic symptoms that are associated with CFP.What is added by this report? Syndromic surveillance systems in Florida identified six adults with CFP following consumption of black grouper. Five patients sought medical attention; health care providers did not make a diagnosis of CFP or report the cases to public health authorities, and none of the patients received treatment. Close collaboration among several investigating agencies allowed traceback efforts to link black grouper consumed by all patients to a common international distributor.What are the implications for public health practice? Syndromic surveillance systems capable of detecting CFP are essential public health tools to identify outbreaks and enhance investigations. Medical and public health practitioners should be educated to inquire about recent fish consumption when evaluating patients with clinically compatible signs and symptoms to allow for prompt treatment, and report suspected CFP cases to public health authorities to facilitate source-food traceback efforts. Public education on avoidance of consumption of relatively large predatory reef fish species known to be from ciguatoxic-endemic areas might reduce the risk for CFP.

  11. Large outbreaks of ciguatera after consumption of brown marbled grouper.

    Science.gov (United States)

    Chan, Thomas Y K

    2014-07-11

    Brown marbled grouper (Epinephelus fuscoguttatus) is an apex predator from coral reefs of the Indo-Pacific region. All five published case series of ciguatera after consumption of brown marbled grouper were reviewed to characterize the types, severity and chronicity of ciguatera symptoms associated with its consumption. Three of these case series were from large outbreaks affecting over 100-200 subjects who had eaten this reef fish served at banquets. Affected subjects generally developed a combination of gastrointestinal, neurological and, less commonly, cardiovascular symptoms. Gastrointestinal symptoms occurred early and generally subsided in 1-2 days. Some neurological symptoms (e.g., paresthesia of four limbs) could last for weeks or months. Sinus bradycardia and hypotension occurred early, but could be severe and prolonged, necessitating the timely use of intravenous fluids, atropine and dopamine. Other cardiovascular and neurological features included atrial ectopics, ventricular ectopics, dyspnea, chest tightness, PR interval >0.2 s, ST segment changes, polymyositis and coma. Concomitant alcohol consumption was associated with a much higher risk of developing bradycardia, hypotension and altered skin sensation. The public should realize that consumption of the high-risk fish (especially the ciguatoxin-rich parts and together with alcohol use) and repeated ciguatoxin exposures will result in more severe and chronic illness.

  12. Characterization of Gambierdiscus lapillus sp. nov. (Gonyaulacales, Dinophyceae): a new toxic dinoflagellate from the Great Barrier Reef (Australia).

    Science.gov (United States)

    Kretzschmar, Anna Liza; Verma, Arjun; Harwood, Tim; Hoppenrath, Mona; Murray, Shauna

    2016-11-25

    Gambierdiscus is a genus of benthic dinoflagellates found worldwide. Some species produce neurotoxins (maitotoxins and ciguatoxins) that bioaccumulate and cause ciguatera fish poisoning (CFP), a potentially fatal food-borne illness that is common worldwide in tropical regions. The investigation of toxigenic species of Gambierdiscus in CFP endemic regions in Australia is necessary as a first step to determine which species of Gambierdiscus are related to CFP cases occurring in this region. In this study, we characterized five strains of Gambierdiscus collected from Heron Island, Australia, a region in which ciguatera is endemic. Clonal cultures were assessed using (i) light microscopy; (ii) scanning electron microscopy; (iii) DNA sequencing based on the nuclear encoded ribosomal 18S and D8-D10 28S regions; (iv) toxicity via mouse bioassay; and (v) toxin profile as determined by Liquid Chromatography-Mass Spectrometry. Both the morphological and phylogenetic data indicated that these strains represent a new species of Gambierdiscus, G. lapillus sp. nov. (plate formula Po, 3', 0a, 7″, 6c, 7-8s, 5‴, 0p, 2″″ and distinctive by size and hatchet-shaped 2' plate). Culture extracts were found to be toxic using the mouse bioassay. Using chemical analysis, it was determined that they did not contain maitotoxin (MTX1) or known algal-derived ciguatoxin analogs (CTX3B, 3C, CTX4A, 4B), but that they contained putative MTX3, and likely other unknown compounds.

  13. An approach to rational ligand-design based on a thermodynamic analysis.

    Science.gov (United States)

    Ui, Mihoko; Tsumoto, Kouhei

    2010-11-01

    Thermodynamic analysis is an effective tool in screening of lead-compounds for development of potential drug candidates. In most cases, a ligand achieve high affinity and specificity to a target protein by means of both favorable enthalpy and entropy terms, which can be reflected in binding profiles of Isothermal Titration Calorimetry (ITC). A favorable enthalpy change suggests the contribution of noncovalent contacts such as hydrogen bonding and van der Waals interaction between a ligand and its target protein. In general, optimization of binding enthalpy is more difficult than that of entropies in ligand-design; therefore, it is desirable to choose firstly a lead-compound based on its binding enthalpic gain. In this paper, we demonstrate the utility of thermodynamic approach to ligand screening using anti-ciguatoxin antibody 10C9 as a model of a target protein which possesses a large hydrophobic pocket. As a result of this screening, we have identified three compounds that could bind to the antigen-binding pocket of 10C9 with a few kcal/mol of favorable binding enthalpy. Comparison of their structure with the proper antigen ciguatoxin CTX3C revealed that 10C9 rigorously identifies their cyclic structure and a characteristic hydroxyl group. ITC measurement might be useful and powerful for a rational ligand screening and the optimization of the ligand; the enthalpic gain is an effective index for ligand-design studies.

  14. Chemical Diversity, Origin, and Analysis of Phycotoxins

    DEFF Research Database (Denmark)

    Rasmussen, Silas Anselm; Andersen, Aaron John Christian; Andersen, Nikolaj Gedsted;

    2016-01-01

    Microalgae, particularly those from the lineage Dinoflagellata, are very well-known for their ability to produce phycotoxins that may accumulate in the marine food chain and eventually cause poisoning in humans. This includes toxins accumulating in shellfish, such as saxitoxin, okadaic acid......, yessotoxins, azaspiracids, brevetoxins, and pinnatoxins. Other toxins, such as ciguatoxins and maitotoxins, accumulate in fish, where, as is the case for the latter compounds, they can be metabolized to even more toxic metabolites. On the other hand, much less is known about the chemical nature of compounds...... complex natural compounds known to mankind, with chemical structures that show no resemblance to what has been characterized from plants, fungi, or bacteria. In addition, it will summarize algal species known to be related to fish-killing blooms, but from which ichthyotoxins are yet to be characterized....

  15. Prevention and control of hazards in seafood

    DEFF Research Database (Denmark)

    Huss, Hans Henrik; Reilly, A.; Embarek, Peter Karim Ben

    2000-01-01

    are listed and discussed. It is pointed out that there are serious safety concerns related to the consumption of raw fish and shellfish due to the presence of biological (bacteria, virus, parasites) and chemical (biotoxins) hazards. These hazards are present in the fish and shellfish pre......Seafood is high on the list of foods transmitting disease. However, the food safety issues are highly focussed and more than 80% of all seafood-borne outbreaks are related to biotoxins (ciguatoxin), scombrotoxin or the consumption of raw molluscan shellfish. The safety hazards in seafood production......-harvest and are difficult or impossible to control by applying presently available preventive measures. In contrast, the hazards related to contamination, recontamination or survival of biological hazards during processing are well-defined and can be controlled by applying Good Manufacturing Practice (GMP), Good Hygiene...

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

    Science.gov (United States)

    Kumar-Roiné, Shilpa; Taiana Darius, H; Matsui, Mariko; Fabre, Nicolas; Haddad, Mohamed; Chinain, Mireille; Pauillac, Serge; Laurent, Dominique

    2011-07-01

    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.

  17. Ciguatera poisoning.

    Science.gov (United States)

    Achaibar, Kira C; Moore, Simon; Bain, Peter G

    2007-10-01

    Ciguatera is a form of poisoning that occurs after eating tropical and subtropical ciguatoxic fish. The ciguatoxins are a family of heat stable, lipid soluble cyclic polyether compounds that bind to and open voltage-sensitive Na(+) channels at resting membrane potential, resulting in neural hyperexcitability, as well as swelling of the nodes of Ranvier. The authors describe a 45-year-old man who developed acute gastrointestinal symptoms in Antigua soon after eating red snapper and grouper, potentially "ciguatoxic fish". This was followed by neurological symptoms 24-48 hours later, including temperature reversal (paradoxical dysaesthesia), intense pruritus and increased nociception as a result of a small fibre peripheral neuropathy. The patient's symptoms and small fibre neuropathy improved over a period of 10 months.

  18. Ciguatoxic Potential of Brown-Marbled Grouper in Relation to Fish Size and Geographical Origin

    Science.gov (United States)

    Chan, Thomas Y. K.

    2015-01-01

    To determine the ciguatoxic potential of brown-marbled grouper (Epinephelus fuscoguttatus) in relation to fish size and geographical origin, this review systematically analyzed: 1) reports of large ciguatera outbreaks and outbreaks with description of the fish size; 2) Pacific ciguatoxin (P-CTX) profiles and levels and mouse bioassay results in fish samples from ciguatera incidents; 3) P-CTX profiles and levels and risk of toxicity in relation to fish size and origin; 4) regulatory measures restricting fish trade and fish size preference of the consumers. P-CTX levels in flesh and size dependency of toxicity indicate that the risk of ciguatera after eating E. fuscoguttatus varies with its geographical origin. For a large-sized grouper, it is necessary to establish legal size limits and control measures to protect public health and prevent overfishing. More risk assessment studies are required for E. fuscoguttatus to determine the size threshold above which the risk of ciguatera significantly increases. PMID:26324735

  19. Severe bradycardia and prolonged hypotension in ciguatera.

    Science.gov (United States)

    Chan, Thomas Yan Keung

    2013-06-01

    Ciguatera results when ciguatoxin-contaminated coral reef fish from tropical or subtropical waters are consumed. The clinical features that present in affected persons are mainly gastrointestinal, neurological, general, and much less commonly, cardiovascular. We report the case of a 50-year-old man who developed the characteristic combination of acute gastrointestinal and neurological symptoms after the consumption of an unidentified coral reef fish head. In addition to those symptoms, he developed dizziness, severe bradycardia (46 bpm) and prolonged hypotension, which required the administration of intravenous atropine and over three days of intravenous fluid replacement with dopamine infusion. Patients with ciguatera can develop severe bradycardia and prolonged hypotension. Physicians should recognise the possible cardiovascular complications of ciguatera and promptly initiate treatment with intravenous atropine, intravenous fluid replacement and inotropic therapy if such complications are observed.

  20. Ciguatera fish poisoning: impact for the military health care provider.

    Science.gov (United States)

    Arnett, Michael V; Lim, Julia T

    2007-09-01

    Ciguatera toxin is a marine neurotoxin produced by microorganisms that becomes concentrated in predatory fish. Toxicity in humans results from the ingestion of contaminated fish harvested in tropical waters. Clinical manifestations of illness include the rapid onset of gastrointestinal symptoms and neurological abnormalities. Because of the rapid onset of symptoms and the potential for case clusters from a common source ingestion of contaminated fish, there is the potential that ciguatera poisoning may initially mimic illnesses caused by antipersonnel biological and chemical agents. We present data on an active duty soldier who presented to sick call for evaluation of new onset paresthesias and was diagnosed with ciguatera toxin poisoning. We also present a review of ciguatera poisoning literature with emphasis on the distinguishing features between ciguatoxin and other neurotoxins of military significance.

  1. Ciguatoxic Potential of Brown-Marbled Grouper in Relation to Fish Size and Geographical Origin.

    Science.gov (United States)

    Chan, Thomas Y K

    2015-11-01

    To determine the ciguatoxic potential of brown-marbled grouper (Epinephelus fuscoguttatus) in relation to fish size and geographical origin, this review systematically analyzed: 1) reports of large ciguatera outbreaks and outbreaks with description of the fish size; 2) Pacific ciguatoxin (P-CTX) profiles and levels and mouse bioassay results in fish samples from ciguatera incidents; 3) P-CTX profiles and levels and risk of toxicity in relation to fish size and origin; 4) regulatory measures restricting fish trade and fish size preference of the consumers. P-CTX levels in flesh and size dependency of toxicity indicate that the risk of ciguatera after eating E. fuscoguttatus varies with its geographical origin. For a large-sized grouper, it is necessary to establish legal size limits and control measures to protect public health and prevent overfishing. More risk assessment studies are required for E. fuscoguttatus to determine the size threshold above which the risk of ciguatera significantly increases.

  2. Assessing the Incidence of Ciguatera Fish Poisoning with Two Surveys Conducted in Culebra, Puerto Rico, during 2005 and 2006

    Science.gov (United States)

    Luber, George; Conklin, Laura; Tosteson, Thomas R.; Granade, Hudson R.; Dickey, Robert W.; Backer, Lorraine C.

    2012-01-01

    Background: Although ciguatera fish poisoning (CFP) is the most common seafood intoxication worldwide, its burden has been difficult to establish because there are no biomarkers to diagnose human exposure. Objective: We explored the incidence of CFP, percentage of CFP case-patients with laboratory-confirmed ciguatoxic meal remnants, cost of CFP illness, and potential risk factors for CFP. Methods: During 2005 and again during 2006, we conducted a census of all occupied households on the island of Culebra, Puerto Rico, where locally caught fish are a staple food. We defined CFP case-patients as persons with gastrointestinal symptoms (abdominal pain, vomiting, diarrhea, or nausea) and neurological symptoms (extremity paresthesia, arthralgia, myalgia, malaise, pruritus, headache, dizziness, metallic taste, visual disturbance, circumoral paresthesia, temperature reversal, or toothache) or systemic symptoms (e.g., bradycardia) within 72 hr of eating fish during the previous year. Participants were asked to save fish remnants eaten by case-patients for ciguatoxin analysis at the Food and Drug Administration laboratory in Dauphin Island, Alabama (USA). Results: We surveyed 340 households during 2005 and 335 households during 2006. The estimated annual incidence of possible CFP was 4.0 per 1,000 person-years, and that of probable CFP was 7.5 per 1,000 person-years. One of three fish samples submitted by probable case-patients was positive for ciguatoxins. None of the case-patients required respiratory support. Households that typically consumed barracuda were more likely to report CFP (p = 0.02). Conclusions: Our estimates, which are consistent with previous studies using similar case findings, contribute to the overall information available to support public health decision making about CFP prevention. PMID:22275728

  3. Neurotoxicity and reactive astrogliosis in the anterior cingulate cortex in acute ciguatera poisoning.

    Science.gov (United States)

    Zhang, Xu; Cao, Bing; Wang, Jun; Liu, Jin; Tung, Vivian Oi Vian; Lam, Paul Kwan Sing; Chan, Leo Lai; Li, Ying

    2013-06-01

    Ciguatoxins (CTXs) cause long-term disturbance of cerebral functions. The primary mechanism of neurotoxicity is related to their interaction with voltage-gated sodium channels. However, until now, the neurological targets for CTXs in the brain of intact animals have not been described. In our study, 1 day following oral exposure to 0.26 ng/g of Pacific ciguatoxin 1 (P-CTX-1), we performed in vivo electrophysiological recordings in the rat anterior cingulate cortex (ACC) and identified the increase in spontaneous firings and enhanced responses to visceral noxious stimulation. Local field recordings characterized the P-CTX-1-induced synaptic potentiation and blockage of the induction of electrical stimulation-induced long-term potentiation in the medial thalamus (MT)-ACC pathway. Furthermore, intracerebroventricular administration of P-CTX-1 at doses of 1.0, 5.0, and 10 nM produced a dose-dependent increase in ACC neuronal firings and MT-ACC synaptic transmission. Further studies showed upregulated Na(+) channel expression in astrocytes under pathological conditions. We hypothesized that the astrocytes might have been activated in the ciguatera poisoning in vivo. Increases in glial fibrillary acid protein expression were detected in reactive astrocytes in the rat ACC. The activation of astroglia was further indicated by activation of the gap junction protein connexin 43 and upregulation of excitatory amino acid transporter 2 expression suggesting that glutamate was normally rapidly cleared from the synaptic cleft during acute ciguatera poisoning. However, neurotoxicity and reactive astrogliosis were not detected in the ACC after 7 days of P-CTX-1 exposure. The present results are the first characterization of P-CTX-1-invoked brain cortex neuronal excitotoxicity in vivo and supported the theme that neuron and astroglia signals might play roles in acute ciguatera poisoning.

  4. Clinical diagnosis and chemical confirmation of ciguatera fish poisoning in New South Wales, Australia.

    Science.gov (United States)

    Farrell, Hazel; Zammit, Anthony; Manning, Jennifer; Shadbolt, Craig; Szabo, Lisa; Harwood, D Tim; McNabb, Paul; Turahui, John A; van den Berg, Debra J

    2016-03-31

    Ciguatera fish poisoning is common in tropical and sub-tropical areas and larger fish (> 10 kg) are more susceptible to toxin accumulation with age. Although the coastal climate of northern New South Wales is considered sub-tropical, prior to 2014 there has only been 1 documented outbreak of ciguatera fish poisoning from fish caught in the region. During February and March 2014, 2 outbreaks of ciguatera fish poisoning involved 4 and 9 individuals, respectively, both following consumption of Spanish mackerel from northern New South Wales coastal waters (Evans Head and Scotts Head). Affected individuals suffered a combination of gastrointestinal and neurological symptoms requiring hospital treatment. At least 1 individual was symptomatic up to 7 months later. Liquid chromatography-tandem mass spectrometry detected the compound Pacific ciguatoxin-1B at levels up to 1.0 µg kg(-1) in fish tissue from both outbreaks. During April 2015, another outbreak of ciguatera fish poisoning was reported in 4 individuals. The fish implicated in the outbreak was caught further south than the 2014 outbreaks (South West Rocks). Fish tissue was unavailable for analysis; however, symptoms were consistent with ciguatera fish poisoning. To our knowledge, these cases are the southernmost confirmed sources of ciguatera fish poisoning in Australia. Educational outreach to the fishing community, in particular recreational fishers was undertaken after the Evans Head outbreak. This highlighted the outbreak, species of fish involved and the range of symptoms associated with ciguatera fish poisoning. Further assessment of the potential for ciguatoxins to occur in previously unaffected locations need to be considered in terms of food safety.

  5. The ladder-shaped polyether toxin gambierol anchors the gating machinery of Kv3.1 channels in the resting state.

    Science.gov (United States)

    Kopljar, Ivan; Labro, Alain J; de Block, Tessa; Rainier, Jon D; Tytgat, Jan; Snyders, Dirk J

    2013-03-01

    Voltage-gated potassium (Kv) and sodium (Nav) channels are key determinants of cellular excitability and serve as targets of neurotoxins. Most marine ciguatoxins potentiate Nav channels and cause ciguatera seafood poisoning. Several ciguatoxins have also been shown to affect Kv channels, and we showed previously that the ladder-shaped polyether toxin gambierol is a potent Kv channel inhibitor. Most likely, gambierol acts via a lipid-exposed binding site, located outside the K(+) permeation pathway. However, the mechanism by which gambierol inhibits Kv channels remained unknown. Using gating and ionic current analysis to investigate how gambierol affected S6 gate opening and voltage-sensing domain (VSD) movements, we show that the resting (closed) channel conformation forms the high-affinity state for gambierol. The voltage dependence of activation was shifted by >120 mV in the depolarizing direction, precluding channel opening in the physiological voltage range. The (early) transitions between the resting and the open state were monitored with gating currents, and provided evidence that strong depolarizations allowed VSD movement up to the activated-not-open state. However, for transition to the fully open (ion-conducting) state, the toxin first needed to dissociate. These dissociation kinetics were markedly accelerated in the activated-not-open state, presumably because this state displayed a much lower affinity for gambierol. A tetrameric concatemer with only one high-affinity binding site still displayed high toxin sensitivity, suggesting that interaction with a single binding site prevented the concerted step required for channel opening. We propose a mechanism whereby gambierol anchors the channel's gating machinery in the resting state, requiring more work from the VSD to open the channel. This mechanism is quite different from the action of classical gating modifier peptides (e.g., hanatoxin). Therefore, polyether toxins open new opportunities in structure

  6. Marine antivenoms.

    Science.gov (United States)

    Currie, Bart J

    2003-01-01

    There is an enormous diversity and complexity of venoms and poisons in marine animals. Fatalities have occurred from envenoming by sea snakes, jellyfish, venomous fish such as stonefish, cone snails, and blue-ringed octopus. Deaths have also followed ingestion of toxins in shellfish, puffer fish (Fugu), and ciguatoxin-containing fish. However antivenoms are generally only available for envenoming by certain sea snakes, the major Australian box jellyfish (Chironex fleckeri) and stonefish. There have been difficulties in characterizing the toxins of C. fleckeri venom, and there are conflicting animals studies on the efficacy of C. fleckeri antivenom. The vast majority of C. fleckeri stings are not life-threatening, with painful skin welts the major finding. However fatalities that do occur usually do so within 5 to 20 minutes of the sting. This unprecedented rapid onset of cardiotoxicity in clinical envenoming suggests that antivenom may need to be given very early (within minutes) and possibly in large doses if a life is to be saved. Forty years of anecdotal experience supports the beneficial effect of stonefish antivenom in relieving the excruciating pain after stonefish spine penetration. It remains uncertain whether stonefish antivenom is efficacious in stings from spines of other venomous fish, and the recommendation of giving the antivenom intramuscularly needs reassessment.

  7. Neurological disease in wild loggerhead sea turtles Caretta caretta.

    Science.gov (United States)

    Jacobson, Elliott R; Homer, Bruce L; Stacy, Brian A; Greiner, Ellis C; Szabo, Nancy J; Chrisman, Cheryl L; Origgi, Francesco; Coberley, Sadie; Foley, Allen M; Landsberg, Jan H; Flewelling, Leanne; Ewing, Ruth Y; Moretti, Richie; Schaf, Susan; Rose, Corinne; Mader, Douglas R; Harman, Glenn R; Manire, Charles A; Mettee, Nancy S; Mizisin, Andrew P; Shelton, G Diane

    2006-06-12

    Beginning in October 2000, subadult loggerhead sea turtles Caretta caretta showing clinical signs of a neurological disorder were found in waters off south Florida, USA. Histopathology indicated generalized and neurologic spirorchiidiasis. In loggerhead sea turtles (LST) with neurospirorchiidiasis, adult trematodes were found in the meninges of the brain and spinal cord of 7 and 3 affected turtles respectively, and multiple encephalic intravascular or perivascular eggs were associated with granulomatous or mixed leukocytic inflammation, vasculitis, edema, axonal degeneration and occasional necrosis. Adult spirorchiids were dissected from meningeal vessels of 2 of 11 LST brains and 1 of 10 spinal cords and were identified as Neospirorchis sp. Affected LST were evaluated for brevetoxins, ciguatoxins, saxitoxins, domoic acid and palytoxin. While tissues from 7 of 20 LST tested positive for brevetoxins, the levels were not considered to be in a range causing acute toxicosis. No known natural (algal blooms) or anthropogenic (pollutant spills) stressors co-occurred with the turtle mortality. While heavy metal toxicosis and organophosphate toxicosis were also investigated as possible causes, there was no evidence for their involvement. We speculate that the clinical signs and pathologic changes seen in the affected LST resulted from combined heavy spirorchiid parasitism and possible chronic exposure to a novel toxin present in the diet of LST.

  8. Global distribution of ciguatera causing dinoflagellates in the genus Gambierdiscus.

    Science.gov (United States)

    Litaker, R Wayne; Vandersea, Mark W; Faust, Maria A; Kibler, Steven R; Nau, Amy W; Holland, William C; Chinain, Mireille; Holmes, Michael J; Tester, Patricia A

    2010-10-01

    Dinoflagellates in the genus Gambierdiscus produce toxins that bioaccumulate in tropical and sub-tropical fishes causing ciguatera fish poisoning (CFP). Little is known about the diversity and distribution of Gambierdiscus species, the degree to which individual species vary in toxicity, and the role each plays in causing CFP. This paper presents the first global distribution of Gambierdiscus species. Phylogenetic analyses of the existing isolates indicate that five species are endemic to the Atlantic (including the Caribbean/West Indies and Gulf of Mexico), five are endemic to the tropical Pacific, and that two species, Gambierdiscus carpenteri and Gambierdiscus caribaeus are globally distributed. The differences in Gambierdiscus species composition in the Atlantic and Pacific correlated with structural differences in the ciguatoxins reported from Atlantic and Pacific fish. This correlation supports the hypothesis that Gambierdiscus species in each region produce different toxin suites. A literature survey indicated a >100-fold variation in toxicity among species compared with a 2 to 9-fold within species variation due to changing growth conditions. These observations suggest that CFP events are driven more by inherent differences in species toxicity than by environmental modulation. How variations in species toxicity may affect the development of an early warning system for CFP is discussed.

  9. Alternative method to detect compounds produced by Gambierdiscus spp.

    Directory of Open Access Journals (Sweden)

    Jon Andoni Sánchez

    2014-06-01

    Full Text Available Ciguatoxins (CTXs and CTX precursors are produced by several Gambierdiscus spp. These polyether toxins are associated to ciguatera fish poisoning (CFP. In addition to CTX, maitotoxins (MTX and gambierol are also produced by these dinoflagellates. MTX mechanism of action is strictly Ca2+ dependent, since the toxin induces a massive cytoplasmatic Ca2+ entrance. However, CTX activates the voltage-dependent sodium channels and no relation with calcium fluxes has been showed. The aim of this work was to study the effect of both toxins in the cytoplasmic calcium levels in the SH-SY5Y neuroblastoma cell line by using the fluorescent probe Fura-2 AM. Two completely different calcium profiles were obtained. While, MTX induces a sustained dose-dependent increase in Fura-2 ratio, CTX produces a light increase in dye ratio. From MTX results a calibration curve concentration versus Fura-2 ratio was obtained where the toxin concentration of an unknown sample can be calculated. Then, the effect of four samples from Gambierdiscus cultures was studied and different calcium profiles were obtained. A high increase in Fura-2 ratio was observed in two samples. The calcium profile was similar to MTX and by using the calibration curve the amount of toxin was calculated (4.9 and 1.8 nM of MTX. In the other samples, from the Fura-2 results the presence of CTX like compounds can be established.

  10. [Imported tropical fish causes ciguatera fish poisoning in Germany].

    Science.gov (United States)

    Zimmermann, Katharina; Eisenblätter, Anneka; Vetter, Irina; Ebbecke, Martin; Friedemann, Miriam; Desel, Herbert

    2015-01-01

    Ciguatera is a seafood-borne illness caused by consumption of tropical fish contaminated with ciguatoxins, lipophilic polyethers that are produced in benthic dinoflagellates and accumulate through the marine food chain. Ciguatera cases in Europe usually occur in travellers returning from tropical and subtropical regions of the Pacific and Carribean, where ciguatera is endemic. In 2012, several cases of ciguatera occurred in Germany due to sale of contaminated fish products originating from the Indian Ocean. Although the symptomatology in these cases were typical of ciguatera, with patients reporting gastrointestinal discomfort including nausea, vomiting and diarrhea as well as neurological effects including widespread intense pruritus, paresthesias, hypothermia or altered temperature sensation and diffuse pain, correct diagnosis was delayed in all cases due to lack of awareness of the treating medical practitioners. In light of increasing global mobility, trade, and occurrence of ciguatoxic fish in previously non-endemic areas, ciguatera should be considered as a possible diagnosis if gastrointestinal and neurological symptoms occur shortly after consumption of fish.

  11. Epidemiology and clinical features of ciguatera fish poisoning in Hong Kong.

    Science.gov (United States)

    Chan, Thomas Y K

    2014-10-20

    In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2) per million people. The groupers have replaced the snappers as the most important cause of ciguatera. Pacific-ciguatoxins (CTX) are most commonly present in reef fish samples implicated in ciguatera outbreaks. In affected subjects, the gastrointestinal symptoms often subside within days, whereas the neurological symptoms can persist for weeks or even months. Bradycardia and hypotension, which can be life-threatening, are common. Treatment of ciguatera is primarily supportive and symptomatic. Intravenous mannitol (1 g/kg) has also been suggested. To prevent ciguatera outbreaks, the public should be educated to avoid eating large coral reef fishes, especially the CTX-rich parts. A Code of Practice on Import and Sale of Live Marine Fish for Human Consumption for Prevention and Control of Ciguatera Fish Poisoning was introduced from 2004 to 2013. The Food Safety Ordinance with a tracing mechanism came into full effect in February 2012. The Government would be able to trace the sources of the fishes more effectively and take prompt action when dealing with ciguatera incidents.

  12. Invasive Lionfish (Pterois volitans: A Potential Human Health Threat for Ciguatera Fish Poisoning in Tropical Waters

    Directory of Open Access Journals (Sweden)

    Alison Robertson

    2013-12-01

    Full Text Available Invasive Indo-Pacific lionfish (Pterois volitans have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP. More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  13. Determination of toxins involved in ciguatera fish poisoning in the Pacific by LC/MS.

    Science.gov (United States)

    Yogi, Kentaro; Sakugawa, Satsuki; Oshiro, Naomasa; Ikehara, Tsuyoshi; Sugiyama, Kiminori; Yasumoto, Takeshi

    2014-01-01

    Ciguatera fish poisoning is the most extensive and difficult to control of the seafood poisonings. To facilitate monitoring of fish toxicity, toxin profiles were investigated by an LC/MS/MS method using 14 reference toxins on eight representative species of fish collected in four different areas of the Pacific. Snappers and groupers from Okinawa contained ciguatoxin-1B (CTX1B) and two deoxy congeners at variable but species-specific ratios, while red snapper, Lutjanus bohar, from Minamitorishima, and amberjack, Seriola dumerili, from Hawaii, contained both CTX1B-type and CTX3C-type toxins. Spotted knifejaw, Oplegnathus punctatus, from Okinawan waters, contained mainly CTX4A and CTX4B, but the same species caught at Miyazaki was contaminated primarily with the CTX3C-type toxins. Otherwise, the toxin profiles were consistently species-specific in fish collected from various locations around Okinawa over 20 years. The LC/MS/MS and mouse bioassay results agreed well, indicating the LC/MS/MS method is a promising alternative to the mouse bioassay. Pure CTX1B and CTX3C were prepared for use in future LC/MS/MS analysis.

  14. Characteristic Features and Contributory Factors in Fatal Ciguatera Fish Poisoning--Implications for Prevention and Public Education.

    Science.gov (United States)

    Chan, Thomas Y K

    2016-04-01

    In this review, the main objective was to describe the characteristic features of fatal ciguatera fish poisoning and identify contributory factors, with a view to promote prevention and public education. Ciguatera-related deaths, although rare, have been reported from the Pacific, Caribbean, and Indian Ocean regions. The clinical features were generally dominated by convulsions and coma, with various focal neurological signs. Several contributory factors could be identified, including consumption of ciguatoxin (CTX)-rich fish parts (viscera and head) in larger amounts, the most ciguatoxic fish species (e.g.,Gymnothorax flavimarginatus) and reef fish collected after storms and individuals' susceptibility. Mass ciguatera fish poisoning with mortalities also occurred when G. flavimarginatus and other ciguatoxic fish species were shared in gatherings and parties. The characteristic features of fatal ciguatera fish poisoning must be recognized early. The public should be repeatedly reminded to avoid eating the most ciguatoxic fish species and the CTX-rich parts of reef fish. To prevent mass poisoning in gatherings and parties, the most ciguatoxic fish species and potentially toxic fish species must be avoided. Particularly after hits by disastrous storms, it is important to monitor the toxicity of reef fish and the incidence rates of ciguatera.

  15. Epidemiology and Clinical Features of Ciguatera Fish Poisoning in Hong Kong

    Directory of Open Access Journals (Sweden)

    Thomas Y. K. Chan

    2014-10-01

    Full Text Available In the present review, the main objective was to describe the epidemiology and clinical features of ciguatera fish poisoning in Hong Kong. From 1989 to 2008, the annual incidence of ciguatera varied between 3.3 and 64.9 (median 10.2 per million people. The groupers have replaced the snappers as the most important cause of ciguatera. Pacific-ciguatoxins (CTX are most commonly present in reef fish samples implicated in ciguatera outbreaks. In affected subjects, the gastrointestinal symptoms often subside within days, whereas the neurological symptoms can persist for weeks or even months. Bradycardia and hypotension, which can be life-threatening, are common. Treatment of ciguatera is primarily supportive and symptomatic. Intravenous mannitol (1 g/kg has also been suggested. To prevent ciguatera outbreaks, the public should be educated to avoid eating large coral reef fishes, especially the CTX-rich parts. A Code of Practice on Import and Sale of Live Marine Fish for Human Consumption for Prevention and Control of Ciguatera Fish Poisoning was introduced from 2004 to 2013. The Food Safety Ordinance with a tracing mechanism came into full effect in February 2012. The Government would be able to trace the sources of the fishes more effectively and take prompt action when dealing with ciguatera incidents.

  16. Emerging tropical diseases in Australia. Part 2. Ciguatera fish poisoning.

    Science.gov (United States)

    Stewart, I; Lewis, R J; Eaglesham, G K; Graham, G C; Poole, S; Craig, S B

    2010-10-01

    Ciguatera poisoning is a food-borne neuro-intoxication caused by consumption of finfish that have accumulated ciguatoxins in their tissues. Ciguatera is a distressing and sometimes disabling condition that presents with a self-limiting though occasionally severe gastro-intestinal illness, progressing to a suite of aberrant sensory symptoms. Recovery can take from days to years; second and subsequent attacks may manifest in a more severe illness. Ciguatera remains largely a pan-tropical disease, although tourism and export fish markets facilitate increased presentation in temperate latitudes. While ciguatera poisoning in the South Pacific was recognised and eloquently described by seafarers in the 18th Century, it remains a public-health challenge in the 21st Century because there is neither a confirmatory diagnostic test nor a reliable, low-cost screening method to ascertain the safety of suspect fish prior to consumption. A specific antidote is not available, so treatment is largely supportive. The most promising pharmacotherapy of recent decades, intravenous mannitol, has experienced a relative decline in acceptance after a randomized, double-blind trial failed to confirm its efficacy. Some questions remain unanswered, however, and the use of mannitol for the treatment of acute ciguatera poisoning arguably deserves revisiting. The immunotoxicology of ciguatera is poorly understood, and some aspects of the epidemiology and symptomatology of ciguatera warrant further enquiry.

  17. Cluster of ciguatera fish poisoning--North Carolina, 2007.

    Science.gov (United States)

    2009-03-27

    Ciguatera fish poisoning (CFP) is a distinctive type of foodborne disease that results from eating predatory ocean fish contaminated with ciguatoxins. As many as 50,000 cases are reported worldwide annually, and the condition is endemic in tropical and subtropical regions of the Pacific basin, Indian Ocean, and Caribbean. In the United States, 5--70 cases per 10,000 persons are estimated to occur yearly in ciguatera-endemic states and territories. CFP can cause gastrointestinal symptoms (nausea, vomiting, abdominal cramps, or diarrhea) within a few hours of eating contaminated fish. Neurologic symptoms, with or without gastrointestinal disturbance, can include fatigue, muscle pain, itching, tingling, and (most characteristically) reversal of hot and cold sensation. This report describes a cluster of nine cases of CFP that occurred in North Carolina in June 2007. Among the nine patients, six experienced reversal of hot and cold sensations, five had neurologic symptoms only, and overall symptoms persisted for more than 6 months in three patients. Among seven patients who were sexually active, six patients also complained of painful intercourse. This report highlights the potential risks of eating contaminated ocean fish. Local and state health departments can train emergency and urgent care physicians in the recognition of CFP and make them aware that symptoms can persist for months to years.

  18. Invasive lionfish (Pterois volitans): a potential human health threat for ciguatera fish poisoning in tropical waters.

    Science.gov (United States)

    Robertson, Alison; Garcia, Ana C; Quintana, Harold A Flores; Smith, Tyler B; Castillo, Bernard F; Reale-Munroe, Kynoch; Gulli, Joseph A; Olsen, David A; Hooe-Rollman, Jennifer I; Jester, Edward L E; Klimek, Brian J; Plakas, Steven M

    2013-12-27

    Invasive Indo-Pacific lionfish (Pterois volitans) have rapidly expanded in the Western Atlantic over the past decade and have had a significant negative impact on reef fish biodiversity, habitat, and community structure, with lionfish out-competing native predators for resources. In an effort to reduce this population explosion, lionfish have been promoted for human consumption in the greater Caribbean region. This study examined whether the geographical expansion of the lionfish into a known ciguatera-endemic region can pose a human health threat for ciguatera fish poisoning (CFP). More than 180 lionfish were collected from waters surrounding the US Virgin Islands throughout 2010 and 2011. Ciguatoxin testing included an in vitro neuroblastoma cytotoxicity assay for composite toxicity assessment of sodium-channel toxins combined with confirmatory liquid chromatography tandem mass spectrometry. A 12% prevalence rate of ciguatoxic lionfish exceeding the FDA guidance level of 0.1 µg/kg C-CTX-1 equivalents was identified in fish from the U.S. Virgin Islands, highlighting a potential consumption risk in this region. This study presents the first evidence that the invasive lionfish, pose a direct human health risk for CFP and highlights the need for awareness and research on this food safety hazard in known endemic areas.

  19. Ciguatera caused by consumption of humphead wrasse.

    Science.gov (United States)

    Chan, Thomas Y K

    2013-12-15

    Humphead wrasse (Cheilinus undulatus) is an apex predator from coral reefs of the Indo-Pacific region. A food surveillance project using a validated mouse bioassay revealed the presence of ciguatoxins in significantly greater amounts in its flesh than in groupers and other coral reef fishes commonly available in Hong Kong wholesale market. Humphead wrasse has long been known to cause ciguatera, but there was a lack of clinical reports. A 45-year-old woman developed ciguatera after eating humphead wrasse. She required ICU care and infusions of intravenous fluids and dopamine for management of severe hypotension. All 5 published case series are also reviewed to characterise the types, severity and chronicity of ciguatera symptoms after its consumption. In addition to the gastrointestinal, neurological and other features that were typical of ciguatera, some subjects developed sinus bradycardia, hypotension, shock, neuropsychiatric features (e.g. mental exhaustion, depression, insomnia and memory loss), other central nervous system symptoms (e.g. coma, convulsions and ataxia) and myocardial ischaemia. Other subjects still experienced residual symptoms 6 months later; these were mainly neurological or neuropsychiatric complaints and skin pruritus. To prevent ciguatera, the public should avoid eating humphead wrasse and other large coral reef fishes. They should realise that consumption of the high-risk fish may result in more severe and chronic illness, including life-threatening complications and neuropsychiatric features.

  20. A new Gambierdiscus species (Dinophyceae) from Rarotonga, Cook Islands: Gambierdiscus cheloniae sp. nov.

    Science.gov (United States)

    Smith, Kirsty F; Rhodes, Lesley; Verma, Arjun; Curley, Belinda G; Harwood, D Tim; Kohli, Gurjeet S; Solomona, Dorothy; Rongo, Teina; Munday, Rex; Murray, Shauna A

    2016-12-01

    Ciguatera fish poisoning (CFP) has been reported for many years in Rarotonga, Cook Islands, and has had the world's highest reported incidence of this illness for the last 20 years. Following intensive sampling to understand the distribution of the causative organisms of CFP, an undescribed Gambierdiscus species was isolated from the Rarotongan lagoon. Gambierdiscus cheloniae sp. nov. has the common Gambierdiscus Kofoidian plate formula (except for a variability in the number of precingular plates in aberrant cells): Po, 3', 6″ (7″), 6C?, 6 or 7S, 5'″, 1p and 2″″. The 2' plate is hatchet shaped and the dorsal end of 1p is pointed and the relatively narrow 1p plate. Morphologically G. cheloniae is similar to the genetically closely related species G. pacificus, G. toxicus and G. belizeanus, although smaller (depth and length) than G. toxicus. The apical pore plate varies from those of G. belizeanus and G. pacificus, which are shorter and narrower, and from G. toxicus, which is larger. G. cheloniae also differs from G. pacificus in the shape of the 2' plate. The description of this new species is supported by phylogenetic analyses using three different gene regions. G. cheloniae produced the putative maitotoxin-3 analogue, MTX-3, but neither maitotoxin or monitored ciguatoxin. Extracts of G. cheloniae were shown to be highly toxic to mice by intraperitoneal (i.p.) injection, although they were less toxic by gavage. It is possible that this species produces toxins other than putative MTX-3.

  1. Analysis of Gambierdiscus transcriptome data supports ancient origins of mixotrophic pathways in dinoflagellates.

    Science.gov (United States)

    Price, Dana C; Farinholt, Natalie; Gates, Colin; Shumaker, Alexander; Wagner, Nicole E; Bienfang, Paul; Bhattacharya, Debashish

    2016-12-01

    Toxic dinoflagellates pose serious threats to human health and to fisheries. The genus Gambierdiscus is significant in this respect because its members produce ciguatoxin that accumulates in predominantly tropical marine food webs and leads to ciguatera fish poisoning. Understanding the biology of toxic dinoflagellates is crucial to developing control strategies. To this end, we generated a de novo transcriptome library from G. caribaeus and studied its growth under different culture conditions to elucidate pathways of carbon (C) and nitrogen (N) utilization. We also gathered available dinoflagellate transcriptome data to trace the evolutionary history of C and N pathways in this phylum. We find that rather than being specific adaptations to the epiphytic lifestyle in G. caribaeus, the majority of dinoflagellates share a large array of genes that putatively confer mixotrophy and the ability to use N via the ornithine-urea cycle and nitric oxide synthase production. These results suggest that prior to plastid endosymbiosis, the dinoflagellate ancestor possessed complex pathways that linked metabolism, intercellular signaling, and stress responses to environmental cues that have been maintained by extant photosynthetic species. This metabolic flexibility likely explains the success of dinoflagellates in marine ecosystems and may presage difficulties in controlling the spread of toxic species.

  2. [First ciguatera outbreak in Germany in 2012].

    Science.gov (United States)

    Friedemann, Miriam

    2016-12-01

    In November 2012, 23 cases of ciguatera with typical combinations of gastrointestinal and neurological symptoms occurred in Germany after consumption of imported tropical fish (Lutjanus spp.). A questionnaire was used to gather information on the disease course and fish consumption. All patients suffered from pathognomonic cold allodynia. Aside from two severe courses of illness, all other cases showed symptoms of moderate intensity. During a three-year follow-up, seven patients reported prolonged paresthesia for more than one year. Two of them reported further neuropathies over almost three years. This is the first time that long-term persistence of symptoms has been documented in detail. Outbreak cases were allocated to eight clusters in seven German cities. A further cluster was prevented by the successful recall of ciguatoxic fish. Three clusters were confirmed by the detection of ciguatoxin in samples of suspicious and recalled fish. An extrapolation on the basis of ciguatoxic samples revealed twenty prevented cases of ciguatera. Further officially unknown cases should be assumed. During the outbreak investigations, inadvertently falsely labelled fish species and fishing capture areas on import and retail level documents were observed. The ascertainment of cases and the outbreak investigations proved to be difficult due to inconsistent case reports to poisons centers, local health and veterinary authorities. In Germany, many physicians are unaware of the disease pattern of ciguatera and the risks caused by tropical fish. The occurrence of further outbreaks during the following years emphasizes the increasing significance of ciguatera in Germany.

  3. An Updated Review of Ciguatera Fish Poisoning: Clinical, Epidemiological, Environmental, and Public Health Management

    Science.gov (United States)

    Friedman, Melissa A.; Fernandez, Mercedes; Backer, Lorraine C.; Dickey, Robert W.; Bernstein, Jeffrey; Schrank, Kathleen; Kibler, Steven; Stephan, Wendy; Gribble, Matthew O.; Bienfang, Paul; Bowen, Robert E.; Degrasse, Stacey; Flores Quintana, Harold A.; Loeffler, Christopher R.; Weisman, Richard; Blythe, Donna; Berdalet, Elisa; Ayyar, Ram; Clarkson-Townsend, Danielle; Swajian, Karen; Benner, Ronald; Brewer, Tom; Fleming, Lora E.

    2017-01-01

    Ciguatera Fish Poisoning (CFP) is the most frequently reported seafood-toxin illness in the world. It causes substantial human health, social, and economic impacts. The illness produces a complex array of gastrointestinal, neurological and neuropsychological, and cardiovascular symptoms, which may last days, weeks, or months. This paper is a general review of CFP including the human health effects of exposure to ciguatoxins (CTXs), diagnosis, human pathophysiology of CFP, treatment, detection of CTXs in fish, epidemiology of the illness, global dimensions, prevention, future directions, and recommendations for clinicians and patients. It updates and expands upon the previous review of CFP published by Friedman et al. (2008) and addresses new insights and relevant emerging global themes such as climate and environmental change, international market issues, and socioeconomic impacts of CFP. It also provides a proposed universal case definition for CFP designed to account for the variability in symptom presentation across different geographic regions. Information that is important but unchanged since the previous review has been reiterated. This article is intended for a broad audience, including resource and fishery managers, commercial and recreational fishers, public health officials, medical professionals, and other interested parties. PMID:28335428

  4. Features of Ciguatera Fish Poisoning Cases in Hong Kong 2004-2007

    Institute of Scientific and Technical Information of China (English)

    CHUN-KWAN WONG; PATRICIA HUNG; KELLIE L.H.LEE; TINA MOK; THOMAS CHUNG; KAI-MAN KAM

    2008-01-01

    To review the clinical features and laboratory investigations of ciguatera patients in Hong Kong between 2004 and 2007 in order to show the timely sampling of implicated fish from ciguatera victims and application of validated mouse bioassay for confirming suspected clinical cases of ciguatera.Methods Diagnosis of the ciguatera victims was based on history of coral fish consumption and clinical presentations stated in official guidelines for clinical diagnosis of ciguatera fish poisoning in Hong Kong.Food remnants of coral fish samples were collected swiftly from ciguatera victims between 2004 and 2007 for ciguatoxins (CTXs) analysis.Results Major clinical symptoms in ciguatera patients included gastrointestinal and neurological effects including limb numbness and diarrhoea,which developed at 0.5 to 15 hours after consumption of fish.In most cases,neurological symptoms were more common than gastrointestinal symptoms.A broad range of attack rate (10%-100%) was observed in each ciguatera outbreak.Validated mouse bioassay on ether extracts of the food remnant samples confirmed that all were CTXs-positive (<0.5-4.3 MU/20 mg ether extract) and directly linked to the corresponding ciguatera cases.Conclusion Consistency between clinical and laboratory analysis for ciguatera poisoning illustrates the application of laboratory mouse bioassay in a timely fashion for confirming ciguatera poisoning cases and implementing effective public health measures.With further improvement in laboratory techniques,features of ciguatera fish poisoning cases can be better defined.Further studies are needed to determine the risk of each class of CTXs (Pacific-,Indian-and Caribbean-CTXs) in Hong Kong.

  5. A phylogenetic re-analysis of groupers with applications for ciguatera fish poisoning.

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    Charlotte Schoelinck

    Full Text Available Ciguatera fish poisoning (CFP is a significant public health problem due to dinoflagellates. It is responsible for one of the highest reported incidence of seafood-borne illness and Groupers are commonly reported as a source of CFP due to their position in the food chain. With the role of recent climate change on harmful algal blooms, CFP cases might become more frequent and more geographically widespread. Since there is no appropriate treatment for CFP, the most efficient solution is to regulate fish consumption. Such a strategy can only work if the fish sold are correctly identified, and it has been repeatedly shown that misidentifications and species substitutions occur in fish markets.We provide here both a DNA-barcoding reference for groupers, and a new phylogenetic reconstruction based on five genes and a comprehensive taxonomical sampling. We analyse the correlation between geographic range of species and their susceptibility to ciguatera accumulation, and the co-occurrence of ciguatoxins in closely related species, using both character mapping and statistical methods.Misidentifications were encountered in public databases, precluding accurate species identifications. Epinephelinae now includes only twelve genera (vs. 15 previously. Comparisons with the ciguatera incidences show that in some genera most species are ciguateric, but statistical tests display only a moderate correlation with the phylogeny. Atlantic species were rarely contaminated, with ciguatera occurrences being restricted to the South Pacific.The recent changes in classification based on the reanalyses of the relationships within Epinephelidae have an impact on the interpretation of the ciguatera distribution in the genera. In this context and to improve the monitoring of fish trade and safety, we need to obtain extensive data on contamination at the species level. Accurate species identifications through DNA barcoding are thus an essential tool in controlling CFP since

  6. Ciguatera fish poisoning in the Pacific Islands (1998 to 2008.

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    Mark P Skinner

    2011-12-01

    Full Text Available BACKGROUND: Ciguatera is a type of fish poisoning that occurs throughout the tropics, particularly in vulnerable island communities such as the developing Pacific Island Countries and Territories (PICTs. After consuming ciguatoxin-contaminated fish, people report a range of acute neurologic, gastrointestinal, and cardiac symptoms, with some experiencing chronic neurologic symptoms lasting weeks to months. Unfortunately, the true extent of illness and its impact on human communities and ecosystem health are still poorly understood. METHODS: A questionnaire was emailed to the Health and Fisheries Authorities of the PICTs to quantify the extent of ciguatera. The data were analyzed using t-test, incidence rate ratios, ranked correlation, and regression analysis. RESULTS: There were 39,677 reported cases from 17 PICTs, with a mean annual incidence of 194 cases per 100,000 people across the region from 1998-2008 compared to the reported annual incidence of 104/100,000 from 1973-1983. There has been a 60% increase in the annual incidence of ciguatera between the two time periods based on PICTs that reported for both time periods. Taking into account under-reporting, in the last 35 years an estimated 500,000 Pacific islanders might have suffered from ciguatera. CONCLUSIONS: This level of incidence exceeds prior ciguatera estimates locally and globally, and raises the status of ciguatera to an acute and chronic illness with major public health significance. To address this significant public health problem, which is expected to increase in parallel with environmental change, well-funded multidisciplinary research teams are needed to translate research advances into practical management solutions.

  7. Ciguatera fish poisoning in Hawai'i and the Pacific.

    Science.gov (United States)

    Copeland, Nathanial K; Palmer, Wyatt R; Bienfang, Paul K

    2014-11-01

    Ciguatera fish poisoning (CFP) is a foodborne illness caused by fish containing ciguatoxin (CTX). The toxin is produced by the microalgae Gambierdiscus spp. which are then eaten by reef fish; humans contract the illness when eating either fish that have eaten the algae, or carnivorous fish that have eaten those fish. CTX is an odorless, tasteless, and colorless neurotoxin that blocks voltage-sensitive Na(+) channels and accumulates in many tissues of the fish, especially the viscera. The illness is typically mild to moderate in severity with gastrointestinal (diarrhea, cramping, nausea, vomiting) and neurological (paraesthesias, cold allodynia, fatigue, pruritis) manifestations. Rarely, the disease can be more severe with significant neuropathic or cardiac effects such as bradycardia and hypotension. Endemic to Hawai'i and islands throughout the Caribbean and Pacific, CFP incidence rates range from several to thousands of cases per 100,000 per year. Since fishing is important for local food supply, exportation, and recreation throughout the Pacific, CFP is medically and economically significant in these areas. We present a case of CFP from Hawai'i to illustrate the disease, demonstrating that the diagnosis is primarily clinical, with confirmatory tests from fish samples available in some cases. Treatment is supportive and symptomatic with no disease specific remedy. The prognosis for most cases is good with a short duration of self-limited symptoms, but for some cases neurological sequelae can become chronic. With no effective treatment, education on which species of reef fish and which body parts to avoid eating is essential in the prevention of CFP.

  8. Ciguatera fish poisoning - New York City, 2010-2011.

    Science.gov (United States)

    2013-02-01

    During August 2010-July 2011, the New York City Department of Health and Mental Hygiene (DOHMH) received reports of six outbreaks and one single case of ciguatera fish poisoning (CFP), involving a total of 28 persons. CFP results from consumption of certain large, predatory, tropical reef fish that have bioaccumulated ciguatoxins (CTX). CFP is characterized by various gastrointestinal, cardiovascular, and neurologic symptoms. A prolonged period of acute illness can result, and the neurologic symptoms can last months, with variable asymptomatic and symptomatic periods. The first two outbreaks and the single case, involving 13 persons, were reported during August 6-September 13, 2010. DOHMH distributed a health alert in November 2010 requesting health-care providers be alert for CFP signs and symptoms. The health alert resulted in identification of 11 more cases that month and an additional two outbreaks involving four persons in July 2011. In comparison, only four CFP outbreaks, involving 21 persons total, had been reported in New York City (NYC) during the preceding 10 years (2000-2009). DOHMH's investigation revealed that 13 persons became ill after eating barracuda, and 15 became ill after eating grouper. Although specific and highly sensitive laboratory analyses can detect and confirm CTX in fish, no practical field tests are available for fish monitoring programs. CFP prevention depends on educating the public, seafood suppliers, and distributors about known CFP endemic areas and high-risk fish species. Traceback investigations of fish associated with outbreaks provide valuable information regarding fishing areas associated with CFP. Not all fish from CFP endemic areas are ciguatoxic, but persons who eat fish from endemic regions are at higher risk for CFP. If an illness is suspected to be CFP, public health authorities should be notified and informed of the case history for possible investigation and intervention measures.

  9. Ciguatera Fish Poisoning in Hawai‘i and the Pacific

    Science.gov (United States)

    Palmer, Wyatt R; Bienfang, Paul K

    2014-01-01

    Ciguatera fish poisoning (CFP) is a foodborne illness caused by fish containing ciguatoxin (CTX). The toxin is produced by the microalgae Gambierdiscus spp. which are then eaten by reef fish; humans contract the illness when eating either fish that have eaten the algae, or carnivorous fish that have eaten those fish. CTX is an odorless, tasteless, and colorless neurotoxin that blocks voltage-sensitive Na+ channels and accumulates in many tissues of the fish, especially the viscera. The illness is typically mild to moderate in severity with gastrointestinal (diarrhea, cramping, nausea, vomiting) and neurological (paraesthesias, cold allodynia, fatigue, pruritis) manifestations. Rarely, the disease can be more severe with significant neuropathic or cardiac effects such as bradycardia and hypotension. Endemic to Hawai‘i and islands throughout the Caribbean and Pacific, CFP incidence rates range from several to thousands of cases per 100,000 per year. Since fishing is important for local food supply, exportation, and recreation throughout the Pacific, CFP is medically and economically significant in these areas. We present a case of CFP from Hawai‘i to illustrate the disease, demonstrating that the diagnosis is primarily clinical, with confirmatory tests from fish samples available in some cases. Treatment is supportive and symptomatic with no disease specific remedy. The prognosis for most cases is good with a short duration of self-limited symptoms, but for some cases neurological sequelae can become chronic. With no effective treatment, education on which species of reef fish and which body parts to avoid eating is essential in the prevention of CFP. PMID:25478299

  10. Neurotoxic Syndromes in Marine Poisonings a Review

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    Gholam Hossein Mohebbi

    2014-08-01

    Full Text Available Background: Marine neurotoxins as of Marine biotoxins are natural toxins that produced mainly by dinoflagellates, diatoms and several species of invertebrates and fish. Marine poisoning results from the ingestion of marine animals contain these toxins and causes considerable adverse effects. Materials and methods: This review provides some facts about the structures of marine neurotoxins, their molecular target and pharmacology, analytical methods for their detection and quantitation, diagnosis and laboratory testing, clinical manifestations, as well as prevention and treatment, if were obtainable. Furthermore, we focus on marine poisoning and various associated neurological syndromes like ciguatera, tetrodotoxin poisoning, and paralytic shellfish poisoning, after ingestion of the common marine toxins. Results: A number of neurotoxins that prescribed according to their potency (LD50 are: Maitotoxin, Ciguatoxins and Palytoxin, Tetrodotoxin and Saxitoxin, Brevetoxins, Azaspiracid, Yessotoxin, Cooliatoxin, Domoic acid and Conotoxins, Respectively. The primary target of most marine neurotoxins is voltage gated sodium channels and the resulting block of ion conductance through these channels. Moreover, these compounds interact with voltage-gated potassium and calcium channels and modulate the flux of stated ions into many cell types. As well, the target recognized for palytoxin is the Na+- K+ /ATPase. Conclusion: Results of reviewed studies revealed that, the Ciguatera is the commonest syndrome of marine poisoning, but is rarely lethal. Puffer fish poisoning results from the ingestion of fish containing tetrodotoxin and paralytic shellfish poisoning are less common, but have a higher fatality rate than ciguatera. Despite their high toxicity, no much research has been done on some of the toxins, like maitotoxin. In addition, there have remained unknown the pharmacological effects, mechanism of action and molecular target of some toxins such as

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

    Science.gov (United States)

    Pawlowiez, Ralph; Darius, Hélène Taiana; Cruchet, Philippe; Rossi, Fanny; Caillaud, Amandine; Laurent, Dominique; Chinain, Mireille

    2013-01-01

    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.

  12. Ecology of the ciguatera causing dinoflagellates from the Northern Great Barrier Reef: changes in community distribution and coastal eutrophication.

    Science.gov (United States)

    Skinner, Mark P; Lewis, Richard J; Morton, Steve

    2013-12-15

    Ciguatera fish poisoning (CFP) is known to be caused by the ciguatoxins from the dinoflagellate genus Gambierdiscus, however, there is the potential for other toxins such as okadaic acid and dinophysistoxins from the genus Prorocentrum, and palytoxin from the genus Ostreopsis, to contaminate seafood. These genera may also be indicators of ecosystem health and potentially impact on coral reef ecosystems and the role they may play in the succession of coral to macroalgae dominated reefs has not been researched. Sixteen GBR field sites spanning inshore, mid-lagoon and outer lagoon (offshore) regions were studied. Samples were collected from September 2006 to December 2007 and abundance of benthic dinoflagellates on different host macroalgae and concentration of nutrients present in the water column were determined. The maximum abundance of Prorocentrum, Ostreopsis and Gambierdiscus found was 112, 793 and 50 cells per gram wet weight of host macroalgae, respectively. The average level of Dissolved Inorganic Nitrogen (DIN) in the water column across all sites (0.03 mg/L) was found to be more than double the threshold critical value (0.013 mg/L) for healthy coral reefs. Compared to a previous study 1984, there is evidence of a major shift in the distribution and abundance of these dinoflagellates. Inshore reefs have either of Prorocentrum (as at Green Island) or Ostreopsis (as at Magnetic Island) dominating the macroalgal surface niche which was once dominated by Gambierdiscus, whilst at offshore regions Gambierdiscus is still dominant. This succession may be linked to the ongoing eutrophication of the GBR lagoon and have consequences for the sources of toxins for ongoing cases of ciguatera.

  13. Ciguatera fish toxicity in French Polynesia: size does not always matter.

    Science.gov (United States)

    Gaboriau, Matthias; Ponton, Dominique; Darius, H Taiana; Chinain, Mireille

    2014-06-01

    Accumulation of ciguatoxins (CTXs) in tropical reef fish tissues during their life is responsible of the most prevalent human seafood intoxication in the South Pacific called Ciguatera Fish Poisoning (CFP). It has been assumed for a long time that CTXs are transferred and accumulated along the trophic food chain, and consequently that smaller individuals within a given fish species are safer to eat than larger ones. However, the relationship between toxicity and fish size has been studied for a limited number of species only and the conclusions are often contradictory. The toxicity of 856 fishes from 59 different species sampled in six islands in French Polynesia between 2003 and 2011 was assessed by Receptor Binding Assay. Among them, 45 species × island and 32 families × island for which the number of individuals was ≥6 allowed testing the relationship between toxicity and size. Except for six specimens of Lutjanus bohar caught in Fakarava (P < 0.01; R(2) = 0.854), the 44 remaining species × island showed no significant increase of CTXs concentration with fish total length (TL). Moreover, the proportion of toxic individuals decreased significantly for Epinephelus polyphekadion from Fakarava (n = 24; P < 0.05) and Kyphosus cinerascens from Raivavae (n = 29; P < 0.05), while no significant variation was detected for the other 43 species × island. At the family level, only three positive and three negative relationships between size and CTXs concentration were observed among the 32 family × island analyzed. No relationship between the proportion of toxic fish within a family and the relative total length of individuals were observed. The lack of relationship between toxicity and size observed for most of the species and families from the six islands suggests that fish size cannot be used as an efficient predictor of fish toxicity in French Polynesia. These results highlight the need for improving our knowledge about metabolic processes

  14. Influence of Environmental Variables on Gambierdiscus spp. (Dinophyceae) Growth and Distribution

    Science.gov (United States)

    Xu, Yixiao; Richlen, Mindy L.; Liefer, Justin D.; Robertson, Alison; Kulis, David; Smith, Tyler B.; Parsons, Michael L.; Anderson, Donald M.

    2016-01-01

    Benthic dinoflagellates in the genus Gambierdiscus produce the ciguatoxin precursors responsible for the occurrence of ciguatera toxicity. The prevalence of ciguatera toxins in fish has been linked to the presence and distribution of toxin-producing species in coral reef ecosystems, which is largely determined by the presence of suitable benthic habitat and environmental conditions favorable for growth. Here using single factor experiments, we examined the effects of salinity, irradiance, and temperature on growth of 17 strains of Gambierdiscus representing eight species/phylotypes (G. belizeanus, G. caribaeus, G. carolinianus, G. carpenteri, G. pacificus, G. silvae, Gambierdiscus sp. type 4–5), most of which were established from either Marakei Island, Republic of Kiribati, or St. Thomas, United States Virgin Island (USVI). Comparable to prior studies, growth rates fell within the range of 0–0.48 divisions day-1. In the salinity and temperature studies, Gambierdiscus responded in a near Gaussian, non-linear manner typical for such studies, with optimal and suboptimal growth occurring in the range of salinities of 25 and 45 and 21.0 and 32.5°C. In the irradiance experiment, no mortality was observed; however, growth rates at 55μmol photons · m-2 · s-1 were lower than those at 110–400μmol photons · m-2 · s-1. At the extremes of the environmental conditions tested, growth rates were highly variable, evidenced by large coefficients of variability. However, significant differences in intraspecific growth rates were typically found only at optimal or near-optimal growth conditions. Polynomial regression analyses showed that maximum growth occurred at salinity and temperature levels of 30.1–38.5 and 23.8–29.2°C, respectively. Gambierdiscus growth patterns varied among species, and within individual species: G. belizeanus, G. caribaeus, G. carpenteri, and G. pacificus generally exhibited a wider range of tolerance to environmental conditions, which may

  15. Invasive Lionfish (Pterosis volitans) Pose Public Health Threats.

    Science.gov (United States)

    Diaz, James H

    2015-01-01

    The lionfish, Pterosis volitans, a native of Indo-Pacific oceans, is a popular saltwater aquarium fish despite venomous spines on its fins. Lionfish were inadvertently introduced into the western Atlantic from Florida in the early 1990s and have overpopulated and dispersed widely into the Caribbean Sea and Gulf of Mexico. Initiatives to control lionfish populations were launched, including the National Oceanographic and Atmospheric Administration (NOAA)-sponsored "Lionfish as Food Campaign".2 Recently, scientists from the Food and Drug Administration (FDA) reported that lionfish caught off the US Virgin Islands contained ciguatoxins and could cause ciguatera fish poisoning (CFP); a seafood-borne poisoning without an antidote or any specific treatment, and a potential for prolonged neurotoxicity. Lionfish pose several public health threats. New strategies to control the lionfish population explosion in coastal waters and offshore fisheries are needed now to ensure seafood safety and public health. The lionfish, Pterosis volitans, is native to the reefs of the western Indian and Pacific Oceans (Figure 1). Brightly colored with red, white, and black stripes and adorned with feathery fins, the lionfish is a popular saltwater aquarium fish despite venomous spines on its fins (Figure 2). Lionfish were introduced into the western North Atlantic from Florida in the early 1990s after some specimens were discarded by dissatisfied amateur aquarists and others escaped from hurricane-flooded public aquariums.1 Since lionfish are voracious carnivores, have few natural predators, and reproduce prolifically, they have overpopulated and dispersed widely from Cape Hatteras to Florida, throughout the Caribbean Sea, and into the Gulf of Mexico.1 The population density of lionfish in its new, invaded territory now exceeds that of its native habitat.1 As a result, campaigns to control lionfish populations were launched in Florida and the Caribbean. Lionfish now pose several public

  16. Effect of gambierol and its tetracyclic and heptacyclic analogues in cultured cerebellar neurons: a structure-activity relationships study.

    Science.gov (United States)

    Pérez, Sheila; Vale, Carmen; Alonso, Eva; Fuwa, Haruhiko; Sasaki, Makoto; Konno, Yu; Goto, Tomomi; Suga, Yuto; Vieytes, Mercedes R; Botana, Luis M

    2012-09-17

    The polycyclic ether class of marine natural products has attracted the attention of researchers due to their complex and large chemical structures and diverse biological activities. Gambierol is a marine polycyclic ether toxin, first isolated along with ciguatoxin congeners from the dinoflagellate Gambierdiscus toxicus. The parent compound gambierol and the analogues evaluated in this work share the main crucial elements for biological activity, previously described to be the C28=C29 double bond within the H ring and the unsaturated side chain [Fuwa, H., Kainuma, N., Tachibana, K., Tsukano, C., Satake, M., and Sasaki, M. (2004) Diverted total synthesis and biological evaluation of gambierol analogues: Elucidation of crucial structural elements for potent toxicity. Chem. Eur. J. 10, 4894-4909]. With the aim to gain a deeper understanding of the cellular mechanisms involved in the biological activity of these compounds, we compared its activity in primary cultured neurons. The three compounds inhibited voltage-gated potassium channels (Kv) in a concentration-dependent manner and with similar potency, caused a small inhibition of voltage-gated sodium channels (Nav), and evoked cytosolic calcium oscillations. Moreover, the three compounds elicited a "loss of function" effect on Kv channels at concentrations of 0.1 nM. Additionally, both the tetracyclic and the heptacyclic derivatives of gambierol elicited synchronous calcium oscillations similar to those previously described for gambierol in cultured cerebellar neurons. Neither gambierol nor its tetracyclic derivative elicited cell toxicity, while the heptacyclic analogue caused a time-dependent decrease in cell viability. Neither the tetracyclic nor the heptacyclic analogues of gambierol exhibited lethality in mice after ip injection of 50 or 80 μg/kg of each compound. Altogether, the results presented in this work support an identical mechanism of action for gambierol and its tetracyclic and heptacyclic analogues

  17. Recent Trends in Marine Phycotoxins from  Australian Coastal Waters

    Directory of Open Access Journals (Sweden)

    Penelope Ajani

    2017-02-01

    Full Text Available Phycotoxins, which are produced by harmful microalgae and bioaccumulate in the  marine food web, are of growing concern for Australia. These harmful algae pose a threat to  ecosystem and human health, as well as constraining the progress of aquaculture, one of the fastest  growing food sectors in the world. With better monitoring, advanced analytical skills and an  increase in microalgal expertise, many phycotoxins have been identified in Australian coastal  waters in recent years. The most concerning of these toxins are ciguatoxin, paralytic shellfish  toxins, okadaic acid and domoic acid, with palytoxin and karlotoxin increasing in significance. The  potential for tetrodotoxin, maitotoxin and palytoxin to contaminate seafood is also of concern,  warranting future investigation. The largest and most significant toxic bloom in Tasmania in 2012  resulted in an estimated total economic loss of~AUD$23M, indicating that there is an imperative to  improve  toxin  and  organism  detection  methods,  clarify  the  toxin  profiles  of  species  of  phytoplankton and carry out both intra‐ and inter‐species toxicity comparisons. Future work also  includes the application of rapid, real‐time molecular assays for the detection of harmful species  and toxin genes. This information, in conjunction with a better understanding of the life histories  and  ecology  of  harmful  bloom  species,  may  lead  to  more  appropriate  management  of  environmental, health and economic resources.

  18. CIGUATERA POISONING: PACIFIC DISEASE, FOODBORNE POISONING FROM FISH IN WARM SEAS AND OCEANS. Review

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    Snezha Zlateva

    2017-02-01

    for months and years, there is a possibility that every medic can encounter its unusual symptoms, requiring specific treatment. The following toxins cause the poisoning: ciguatoxin, meitotoxin, ostreotoxin, domoic acid and some other unspecified toxins. They are lipid soluble, thermo stable and cannot be decomposed by culinary processing. These toxins have neurotoxic, cardiotoxic, hemolytic properties and cause diarrheic syndrome. Clinical presentation is characterized by average latent period of 12 hours after the consummation, vomiting and diarrhea next 24 hours and neurological symptoms that appear at the beginning of the poisoning with paresthesias along the body, changing feeling of hot and cold, strong myalgia. Disturbances in cardiac rhythm and conduction, strong dehydration or shock are possible in severe cases. Light cases pass over in several days, but, more often the poisoning has a chronic course – from 3-4 months to 1 year, with prevalence of neurologic symptoms: myalgia, paresthesias, skin itching with scratches, depression. The management is not specific and includes stomach lavage with activated charcoal, fluids replacement during the first 24 hours, corticosteroids, antiallergics, high doses of vitamins from group B (Vit. B1, Vit. B6, Vit. B12, mannitol IV, nootropic medicaments, antidepressants and other symptomatic medicaments. The prophylaxis is done by examining every fish with specific test for detecting ciguateratoxin.