ciguatoxins and maitotoxin

Marine polycyclic ether natural products have gained significant interest from the chemical community due to their impressively huge molecular architecture and diverse biological functions. The structure assignment of this class of extraordinarily complex natural products has mainly relied on NMR spectroscopic analysis. However, NMR spectroscopic analysis has its own limitations, including configurational assignment of stereogenic centers within conformationally flexible systems. Chemical shift deviation analysis of synthetic model compounds is a reliable means to assign the relative configuration of "difficult" stereogenic centers. The complete configurational assignment must be ultimately established through total synthesis. The aim of this review is to summarize the indispensable role of organic synthesis in stereochemical assignment of marine polycyclic ethers.

Topics: Aquatic Organisms; Chemistry Techniques, Synthetic; Ciguatoxins; Ethers; Ethers, Cyclic; Humans; Magnetic Resonance Spectroscopy; Marine Toxins; Molecular Structure; Oxocins; Polymers; Secondary Metabolism; Stereoisomerism; Structure-Activity Relationship

Ciguatoxins (CTX) and brevetoxins (BTX) are polycyclic ethereal compounds biosynthesized by the worldwide distributed planktonic and epibenthic dinoflagellates of

Topics: Animals; Ciguatera Poisoning; Ciguatoxins; Dinoflagellida; Humans; Ligands; Marine Toxins; Oxocins; Potassium Channels, Voltage-Gated

Since the isolation of brevetoxin-B, a red tide toxin, many bioactive marine natural products featuring synthetically challenging trans-fused polycyclic ether ring systems have been reported. We have developed SmI(2)-induced cyclization of beta-alkoxyacrylate with aldehyde, affording 2,6-syn-2,3-trans-tetrahydropyran (THP) or 2,7-syn-2,3-trans-oxepane with complete stereoselection, as a key reaction of efficient iterative and bi-directional strategies for the construction of these polycyclic ethers. This reaction is also applicable to the synthesis of 3-, 5-, and 6-methyl-THPs and 3,5-dimethyl-THP. The synthesis of 2-methyl- and 2,6-dimethyl-THPs was accomplished by means of a unique methyl insertion. Recently, the SmI(2)-induced cyclization was extended to similar reactions using beta-alkoxyvinyl sulfone and sulfoxide. Reaction of (E)- and (Z)-beta-alkoxyvinyl sulfone-aldehyde afforded 2,6-syn-2,3-trans- and 2,6-syn-2,3-cis- THPs, respectively. Reaction of (E)-beta-alkoxyvinyl (R)- and (S)-sulfoxides gave 2,6-anti-2,3-cis- and 2,6-syn-2,3-trans-THPs, respectively. Reaction of (Z)-beta-alkoxyvinyl (R)-sulfoxides gave 2,6-syn-2,3-cis-THP and an olefinic product, while that of (Z)-beta-alkoxyvinyl (S)-sulfoxide afforded a mixture of many products. These SmI(2)-induced cyclizations have been applied to the total syntheses of various natural products, including brevetoxin-B, mucocin, pyranicin, and pyragonicin. Synthetic studies on gambierol and maitotoxin are also introduced.

Topics: Biological Products; Ciguatoxins; Cyclization; Ethers; Heterocyclic Compounds, 4 or More Rings; Iodides; Lactones; Marine Toxins; Oxocins; Polymers; Pyrans; Samarium

Synapses are specialised structures where interneuronal communication takes place. Not only brain function is absolutely dependent on synaptic activity, but also most of our organs are intimately controlled by synaptic activity. Synapses re therefore an ideal target to act upon and poisonous species have evolved fascinating neurotoxins capable of shutting down neuronal communication by blocking or activating essential components of the synapse. By hijacking key proteins of the communication machinery, neurotoxins are therefore extremely valuable tools that have, in turn, greatly helped our understanding of synaptic biology. Moreover, analysis and understanding of the molecular strategy used by certain neurotoxins has allowed the design of entirely new classes of drugs acting on specific targets with high selectivity and efficacy. This chapter will discuss the different classes of marine neurotoxins, their effects on neurotransmitter release and how they act to incapacitate key steps in the process leading to synaptic vesicle fusion.

Topics: Acrylamides; Amino Acid Sequence; Animals; Calcium Channel Blockers; Calcium Channels; Ciguatoxins; Cnidarian Venoms; Ion Channels; Marine Toxins; Models, Molecular; Molecular Sequence Data; Neurotoxins; Neurotransmitter Agents; Oxocins; Potassium Channels; Saxitoxin; Sea Anemones; Synaptic Transmission; Tetrodotoxin

The unprecedented structure of the marine natural product brevetoxin B was elucidated by the research group of Nakanishi and Clardy in 1981. The ladderlike molecular architecture of this fused polyether molecule, its potent toxicity, and fascinating voltage-sensitive sodium channel based mechanism of action immediately captured the imagination of synthetic chemists. Synthetic endeavors resulted in numerous new methods and strategies for the construction of cyclic ethers, and culminated in several impressive total syntheses of this molecule and some of its equally challenging siblings. Of the marine polyethers, maitotoxin is not only the most complex and most toxic of the class, but is also the largest nonpolymeric natural product known to date. This Review begins with a brief history of the isolation of these biotoxins and highlights their biological properties and mechanism of action. Chemical syntheses are then described, with particular emphasis on new methods developed and applied to the total syntheses. The Review ends with a discussion of the, as yet unfinished, story of maitotoxin, and projects into the future of this area of research.

Topics: Animals; Ciguatoxins; Cyclization; Ethers; Marine Toxins; Molecular Structure; Oxocins

Topics: Bacterial Toxins; Ciguatoxins; Cyanobacteria Toxins; Ethers, Cyclic; Marine Toxins; Microcystins; Okadaic Acid; Oxocins; Peptides, Cyclic

Topics: Cell Size; Ciguatera Poisoning; Ciguatoxins; Dinoflagellida; Humans; Oxocins

Over the last decade, knowledge has significantly increased on the taxonomic identity and distribution of dinoflagellates of the genera

Topics: Atlantic Ocean; Chromatography, High Pressure Liquid; Ciguatoxins; Dinoflagellida; Marine Toxins; Mediterranean Sea; Oxocins; Seawater; Spectrometry, Mass, Electrospray Ionization; Tandem Mass Spectrometry; Water Microbiology

Ciguatera fish poisoning is a serious human health issue that is highly localized to tropical and sub-tropical coastal areas, affecting many of the indigenous island communities intrinsically linked to reef systems for sustenance and trade. It is caused by the consumption of reef fish contaminated with ciguatoxins and is reported as the most common cause of non-bacterial food poisoning. The causative toxins bioaccumulate up the food web, from small herbivorous fish that graze on microalgae of the genus Gambierdiscus into the higher trophic level omnivorous and carnivorous fish predating on them. The number of Gambierdiscus species being described is increasing rapidly and the role of other toxins produced by this microalgal genus in ciguatera intoxications, such as maitotoxin, remains unclear. Ciguatoxins and maitotoxin are among the most potent marine toxins known and there are currently no methods of analysis that can simultaneously monitor these toxins with a high degree of specificity. To meet this need a rapid and selective ultra-performance liquid chromatography tandem mass spectrometry method has been developed to rapidly screen Gambierdiscus cultures and environmental sample device extracts for ciguatoxins and maitotoxins. A fast sample preparation method has also been developed to allow sensitive quantification of the potent ciguatoxin fish metabolite P-CTX-1B from fish extracts, and this method has been subjected to a small validation study. Novel aspects of this approach include the use of alkaline mobile phase for chromatographic separation and specific monitoring of the various toxins. This method has good potential to help evaluate ciguatera risk associated with Gambierdiscus and related microalgal species, and to help promote method development activities for this important and analytically challenging toxin class.

Topics: Animals; Chromatography, Liquid; Ciguatoxins; Environmental Monitoring; Fishes; Marine Toxins; Oxocins; Tandem Mass Spectrometry

Species in the epi-benthic dinoflagellate genus Gambierdiscus produce ciguatoxins (CTXs) and maitotoxins (MTXs), which are among the most potent marine toxins known. Consumption of fish contaminated with sufficient quantities of CTXs causes Ciguatera Fish Poisoning (CFP), the largest cause of non-bacterial food poisoning worldwide. Maitotoxins, which can be found in the digestive system of fish, could also contribute to CFP if such tissues are consumed. Recently, an increasing number of Gambierdiscus species have been identified; yet, little is known about the variation in toxicity among Gambierdiscus strains or species. This study is the first assessment of relative CTX- and MTX-toxicity of Gambierdiscus species from areas as widespread as the North-Eastern Atlantic Ocean, Pacific Ocean and the Mediterranean Sea. A total of 13 strains were screened: (i) seven Pacific strains of G. australes, G. balechii, G. caribaeus, G. carpenteri, G. pacificus, G. scabrosus and one strain of an undetermined species (Gambierdiscus sp. Viet Nam), (ii) five strains from the North-Eastern Atlantic Ocean (two G. australes, a single G. excentricus and two G. silvae strains), and (iii) one G. carolinianus strain from the Mediterranean Sea. Cell pellets of Gambierdiscus were extracted with methanol and the crude extracts partitioned into a CTX-containing dichloromethane fraction and a MTX-containing aqueous methanol fraction. CTX-toxicity was estimated using the neuro-2a cytoxicity assay, and MTX-toxicity via a human erythrocyte lysis assay. Different species were grouped into different ratios of CTX- and MTX-toxicity, however, the ratio was not related to the geographical origin of species (Atlantic, Mediterranean, Pacific). All strains showed MTX-toxicity, ranging from 1.5 to 86pg MTX equivalents (eq) cell

Topics: Animals; Biological Assay; Ciguatera Poisoning; Ciguatoxins; Dinoflagellida; Erythrocytes; Marine Toxins; Oxocins; Phylogeny

Two isolates of a new tropical, epiphytic dinoflagellate species, Gambierdiscus honu sp. nov., were obtained from macroalgae sampled in Rarotonga, Cook Islands, and from North Meyer Island, Kermadec Islands. Gambierdiscus honu sp. nov. had the common Gambierdiscus Kofoidian plate formula: Po, 3', 6″, 6C?, 6 or 7S, 5‴, 1p and 2⁗. The characteristic morphological features of this species were its relatively small short dorsoventral length and width and the shape of individual plates, in particular the combination of the hatchet-shaped 2' and pentagonal 3' plates and the length to width ratio of the antapical 1p plate. The combination of these characteristics plus the smooth thecal surface and equal sized 1⁗ and 2⁗ plates differentiated this species from other Gambierdiscus species. The phylogenetic analyses supported the unique description. Both isolates of G. honu produced the putative maitotoxin (MTX)-3 analogue, but neither produced ciguatoxin (CTX) or MTX. Extracts of G. honu were shown to be highly toxic to mice by intraperitoneal injection (0.2mg/kg), although less toxic by gavage. It is possible that toxins other than putative MTX-3 are produced.

Topics: Animals; Ciguatoxins; Complex Mixtures; Dinoflagellida; Injections, Intraperitoneal; Marine Toxins; Mice; Oxocins; Phylogeny; Polynesia; Seaweed

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.

Topics: Animals; Australia; Ciguatera Poisoning; Ciguatoxins; Dinoflagellida; Marine Toxins; Oxocins; Phylogeny; Sequence Analysis, DNA

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.. 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.. 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.. 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.

Topics: Animals; Biological Assay; Cell Line, Tumor; Chromatography, High Pressure Liquid; Ciguatoxins; Dinoflagellida; Humans; Marine Toxins; Oxocins; Pacific Ocean; Spectrometry, Fluorescence

Ciguatoxins (CTXs) and maitotoxins (MTXs) are polyether ladder shaped toxins derived from the dinoflagellate Gambierdiscus toxicus. Despite the fact that MTXs are 3 times larger than CTXs, part of the structure of MTXs resembles that of CTXs. To date, the synthetic ciguatoxin, CTX 3C has been reported to activate voltage-gated sodium channels, whereas the main effect of MTX is inducing calcium influx into the cell leading to cell death. However, there is a lack of information regarding the effects of these toxins in a common cellular model. Here, in order to have an overview of the main effects of these toxins in mice cortical neurons, we examined the effects of MTX and the synthetic ciguatoxin CTX 3C on the main voltage dependent ion channels in neurons, sodium, potassium, and calcium channels as well as on membrane potential, cytosolic calcium concentration ([Ca(2+)]c), intracellular pH (pHi), and neuronal viability. Regarding voltage-gated ion channels, neither CTX 3C nor MTX affected voltage-gated calcium or potassium channels, but while CTX 3C had a large effect on voltage-gated sodium channels (VGSC) by shifting the activation and inactivation curves to more hyperpolarized potentials and decreasing peak sodium channel amplitude, MTX, at 5 nM, had no effect on VGSC activation and inactivation but decreased peak sodium current amplitude. Other major differences between both toxins were the massive calcium influx and intracellular acidification produced by MTX but not by CTX 3C. Indeed, the novel finding that MTX produces acidosis supports a pathway recently described in which MTX produces calcium influx via the sodium-hydrogen exchanger (NHX). For the first time, we found that VGSC blockers partially blocked the MTX-induced calcium influx, intracellular acidification, and protected against the short-term MTX-induced cytotoxicity. The results presented here provide the first report that shows the comparative effects of two prototypical ciguatera toxins, CTX 3C and MTX, in a neuronal model. We hypothesize that the analogies and differences in the bioactivity of these two toxins, produced by the same microorganism, may be strongly linked to their chemical structure.

Topics: Animals; Calcium; Calcium Channels; Cell Survival; Cells, Cultured; Ciguatoxins; Hydrogen-Ion Concentration; Marine Toxins; Membrane Potentials; Mice; Neurons; Oxocins; Patch-Clamp Techniques; Sodium Channels; Sodium-Hydrogen Exchangers

[structure: see text]. The stereoselective syntheses of the C'D'E'F'-ring system of maitotoxin and the FG-ring system of gambierol were accomplished. The key steps involve 6-endo-cyclization of methylepoxide, SmI2-induced reductive cyclization, 6-endo-cyclization of vinylepoxide, and formation of the lactone ring.

Topics: Ciguatoxins; Ethers, Cyclic; Marine Toxins; Molecular Structure; Oxocins; Polycyclic Compounds; Stereoisomerism

Human consumption of over 400 species of tropical fish containing polyether toxins (e.g. ciguatoxins, maitotoxins) causes ciguatera fish poisoning. The Caribbean barracuda (Sphyraena barracuda) is one of the most potent ciguatoxic fish. The objective of this study was to determine whether toxicity of 14 barracuda livers was correlated with lipid peroxidation. A significant correlation (p = 0.015, Pearson's correlation) between lipid peroxidation and toxicity of barracuda liver was found. Because iron and copper are well-known catalysts of hydroxyl radical production and lipid peroxidation in biological systems, the correlation between the concentrations of these metals in barracuda liver and lipid peroxidation and toxicity was also investigated. Cadmium was significantly correlated (p = 0.014) with the toxicity of barracuda livers. This study provides the first data concerning the concentration of iron, copper, and cadmium in the liver of the Caribbean barracuda. Of the three metals studied in barracuda liver, iron was the most abundant, followed by copper and cadmium. Lipid peroxidation was highly variable and detected in five (36%) of the liver samples. Lipid peroxidation was not statistically significantly correlated (p > 0.05) with concentrations of iron, copper, and cadmium in barracuda liver. Collectively, these findings provide additional evidence that lipid peroxidation can be a mechanistic component of ciguatera toxicity in the Caribbean barracuda.

Topics: Animals; Caribbean Region; Chromatography, High Pressure Liquid; Ciguatoxins; Fishes; Lipid Peroxidation; Liver; Malondialdehyde; Marine Toxins; Metals, Heavy; Oxocins; Sensitivity and Specificity; Tumor Cells, Cultured

We have modified the cell-based directed cytotoxicity assay for sodium channel and calcium channel active phycotoxins using a c-fos-luciferase reporter gene construct. In this report we describe the conceptual basis to the development of reporter gene assays for algal-derived toxins and summarize both published and unpublished data using this method. N2A mouse neuroblastoma cells, which express voltage-dependent sodium channels, were stably transfected with the reporter gene c-fos-luc, which contains the firefly luciferase gene under the transcriptional regulation of the human c-fos response element. The characteristics of the N2A reporter gene assay were determined by dose response with brevetoxin and ciguatoxin. Brevetoxin-1 and ciguatoxin-1 induced c-fos-luc with an EC50 of 4.6 and 3.0 ng ml(-1), respectively. Saxitoxin caused a concentration-dependent inhibition of brevetoxin-1 induction of c-fos-luc with an EC50 of 3.5 ng ml(-1). GH4C1 rat pituitary cells, which lack voltage-dependent sodium channels but express voltage-dependent calcium channels, were also stably transfected with the c-fos-luc. GH4C1 cells expressing c-fos-luciferase were responsive to maitotoxin (1 ng ml(-1)) and a putative toxin produced by Pfiesteria piscicida. Although reporter gene assays are not designed to replace existing detection methods used to measure toxin activity in seafood, they do provide a valuable means to screen algal cultures for toxin activity, to conduct assay-guided fractionation and to characterize pharmacologic properties of algal toxins.

Topics: Animals; Biological Assay; Ciguatoxins; Dose-Response Relationship, Drug; Genes, fos; Genes, Reporter; Luciferases; Marine Toxins; Mice; Neuroblastoma; Neurotoxins; Oxocins; Pfiesteria piscicida; Pituitary Gland; Proto-Oncogene Proteins c-fos; Rats; RNA, Messenger; Saxitoxin; Transfection; Tumor Cells, Cultured

A range of marine polyether toxins from dinoflagellates were analysed by ionspray mass spectrometry. Ciguatoxin-1 ([M+H]+ m/z = 1,111.8) purified from several fish species yielded singly charged ions corresponding to the parent ion, sodium and H2O adducts and ions for the loss of up to five H2O molecules. Ciguatoxin-1 was detected to 1 ng; however, interference from fish lipids precluded direct detection of ciguatoxin-1 in crude extracts from fish flesh spiked with ciguatoxin-1 at a level equivalent to 1.5 ng ciguatoxin-1/g of extracted flesh. Maitotoxin-2 yielded doubly and triply charged ions for sodium and potassium salts and likely possessed only one sulphate ester (M(r) = 3,298 for the mono-sodium salt). Maitotoxin-3, a recently isolated small maitotoxin, yielded singly charged ions including ions for the loss of one sulphate and up to four H2O molecules. Maitotoxin-3 is proposed to be a polyether compound possessing two sulphate esters (M(r) = 1,060.5 for the disodium salt). Brevetoxin-A ([M+H]+ m/z = 867.5) and brevetoxin-B ([M+H]+ m/z = 895.5) yielded singly charged ions corresponding to the parent ion, Na+ adducts and the loss of up to four H2O molecules. Okadaic acid ([M+H]+ m/z = 805.5) yielded singly charged ions corresponding to the parent ion and ions for the loss of up to three H2O molecules. A signal for M + 18 Da species that may represent [M+NH4]+ was observed for ciguatoxin-1, brevetoxin-A and -B, and okadaic acid. For all polyethers examined, the orifice potential influenced the relative intensity of the ions detected in a predictable manner.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Carcinogens; Chromatography, High Pressure Liquid; Ciguatoxins; Dinoflagellida; Eels; Ethers, Cyclic; Fishes; Marine Toxins; Mass Spectrometry; Okadaic Acid; Oxocins; Spectrometry, Mass, Fast Atom Bombardment

Ciguatoxin-like, scaritoxin-like and other unidentified lipid-soluble toxins were detected in a specimen of Scomberomorus commersoni captured in sub-tropical Queensland. The fish was from a batch that had been involved in human poisonings. The ciguatoxin-like substance made a greater contribution to the total toxicity than did the scaritoxin-like substance. Water-soluble toxins were also present. The most important of these in terms of contribution to total toxicity was unidentified toxic material present in fractions eluted from a silicic acid column with 100% methanol or methanol:water (1:1). After TLC this material yielded a spot positive for alkaloids. Maitotoxin was also detected among the water-soluble toxins. The lethal potency of the fish flesh approximated 27.3 MU/100 g of flesh with water-soluble toxins contributing to a greater extent than the lipid-soluble toxins. (A MU is defined as the minimum amount of toxic material expressed in g required to kill a 20 g mouse within 24 hr after i.p. injection.) The 15 kg fish studied contained a total of approximately 4095 MU. The presence of several water-soluble and lipid-soluble toxins in the fish has implications for the detection of such ciguateric fishes and for the diagnosis and treatment of poisonings stemming from ingestion of these fishes.

Topics: Animals; Chromatography, Thin Layer; Ciguatoxins; Electrophoresis, Cellulose Acetate; Fishes; Guinea Pigs; Humans; Ileum; In Vitro Techniques; Lethal Dose 50; Marine Toxins; Mice; Muscle Contraction; Muscle, Smooth; Oxocins; Solubility

Seven clonal strains of Gambierdiscus toxicus isolated from three ciguateric areas around Tahiti island were mass cultured and extracted for ciguatoxins and maitotoxin. CTX analogs were detected only in one clone (GTP1), suggesting that CTX production may be strain-dependent. However, this in vitro production of CTXs, which remains fairly poor with regards to the toxicity levels encountered in wild G. toxicus, is not a stable temporal characteristic. On the other hand, maitotoxic compounds were detected in all 7 strains in copious amount, especially in clone GTH2.

Topics: Animals; Cells, Cultured; Ciguatoxins; Dinoflagellida; Marine Toxins; Mice; Oxocins; Polynesia; Species Specificity

This study examined the development of a highly simplified solid-phase colored latex immunobead assay for the detection of ciguatoxin and related polyethers. This procedure was compared with the stick enzyme immunoassay previously reported. Chi-square analysis of two separate experiments on 153 and 283 fish of various species gave chi 2 values of p less than 0.001 and p less than 0.005, respectively. Agreement between the two procedures with 26 fish implicated in ciguatera poisoning was 100%. A preliminary assessment in the field showed encouraging results. The procedure appears to be simple and applicable to field use. Furthermore, this procedure should be applicable to other antibody-antigen detections, especially low dalton determinations.

Topics: Animals; Ciguatoxins; Fishes; Humans; Immunoassay; Marine Toxins; Monensin; Oxocins

Ciguatoxin and maitotoxin, extracted from a species of moray-eel, Gymnothorax javanicus, and from a wild dinoflagellate, Gambierdiscus toxicus, were tested on rat atria and rabbit duodenum. Biphasic inotropic and chronotropic responses with excitatory and inhibitory components were observed. The effects of agents such as reserpine, propranolol, phentolamine, atropine and manganese ions were investigated. We conclude that, at the dosage levels used, ciguatoxin acts mainly at the nerve endings, while maitotoxin exerts prominent toxic effects on muscles.

Topics: Animals; Atropine; Ciguatoxins; Duodenum; Guinea Pigs; Heart; Heart Rate; In Vitro Techniques; Marine Toxins; Muscle Contraction; Muscle, Smooth; Myocardial Contraction; Oxocins; Rabbits; Rats; Receptors, Muscarinic

The effects of ciguatoxin, scaritoxin and maitotoxin, the main toxins involved in ciguatera fish poisoning, has been studied in pentobarbital anaesthetized cats. Intravenous injections of increasing doses of these toxins (5 to 160 microgram/kg of partially purified samples) evoked respiratory and cardiovascular disturbances: hyperventilation at low doses and respiratory depression leading to respiratory arrest at high doses; bradycardia and troubles of the atrioventricular conduction at low doses, arrhythmias and ventricular tachycardia with transient hypertension at sublethal doses, and falling arterial pressure leading to complete heart failure at high doses. The mode of action of ciguatoxin has been studied by testing the preventive effects of pharmacological compounds such as hexamethonium, atropine, propranolol and phentolamine and by proceeding to bilateral adrenalectomy. The results have indicated both central and peripheral effects. Cholinergic and also alpha-adrenergic actions were pointed out.

Topics: Adrenalectomy; Animals; Atropine; Blood Pressure; Cats; Ciguatoxins; Heart Rate; Hexamethonium Compounds; Marine Toxins; Oxocins; Propranolol; Respiration

The effects of ciguatoxin (CT) and maitotoxin (MT) were studied on the isolated atria of the guinea pig. Application of CT evoked a prolonged positive inotropic effect on the electrically-driven atria and both inotropic and chronotropic effects on the spontaneously-beating right atria. The response to MT in contrast was biphasic. At low concentration (10(-8) Gm per ml) MT enhanced the atrial contractility, while at higher concentrations (5 x 10(-8) Gm per ml) it depressed the atria and frequently to a standstill. The results indicate that CT and MT have a direct action on the contractile mechanism of the heart and their effects are readily distinguishable.

Topics: Animals; Ciguatoxins; Eels; Female; Guinea Pigs; Heart; Heart Atria; In Vitro Techniques; Male; Marine Toxins; Myocardial Contraction; Oxocins