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At least 253 records · Page 14Linked to original sources
PubMed1991

An enzyme immunoassay for the detection of Florida red tide brevetoxins.

A non-competitive solid-phase enzyme immunoassay for detection of brevetoxins in various matrices has been developed. The assay utilizes antibodies raised in a goat against brevetoxin PbTx-3-keyhole limpet hemocyanin conjugates with specific purification of brevetoxin antibodies through protein G and brevetoxin affinity columns, and rabbit anti-goat antibodies covalently linked to horseradish peroxidase. The assay was used specifically to detect brevetoxins in both cell culture and contaminated tissues. Sensitivity of the assay is 0.04 picomolar, and toxin can be quantified from 0.04 pM to 0.4 pM brevetoxin per well in microtiter plates by comparison with standard curves.

Animals↗
PubMed1993

Distribution and elimination of ingested brevetoxin (PbTx-3) in rats.

As a first step towards understanding the pathologic effects of ingested brevetoxin (PbTx) in marine mammals, we determined how [3H]PbTx-3 was distributed and eliminated when ingested at sub-lethal dosages (18.6 micrograms/kg) by Fischer 344 rats. Brevetoxin was distributed widely in the body, but concentrated primarily in the liver. It was eliminated in equivalent quantities through the urine and feces. However, we believe urinary clearance is the primary route for PbTx-3 absorbed from the gastrointestinal tract.

Animals↗
PubMed1993

Multiple toxins in a specimen of the narrow-barred Spanish mackerel, Scomberomorus commersoni.

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.

Animals↗
PubMed1986

The maitotoxin-evoked Ca2+ entry into synaptosomes is enhanced by cholera toxin.

Effects of the Gs protein-mediated adenylate cyclase facilitatory system on Ca2+ entry into synaptosomes were studied, using two specific toxins. A putative Ca2+-channel agonist, maitotoxin (MTX), increased the 45Ca2+ entry and [Ca2+]i, determined with Quin-II, into synaptosomes of the rat brainstem, which were not attenuated by nifedipine. However, another Ca2+-channel agonist, BAY K-8644 did not alter the 45Ca2+ entry nor [Ca2+]i. The MTX-induced increase of the 45Ca2+ entry was significantly enhanced by addition of dibutyryl cyclic adenosine monophosphate and by the pretreatment with cholera toxin. These findings support the view that stimulation of presynaptic receptors coupled to the Gs-adenylate cyclase system may lead to a facilitation of the release of neurotransmitters, through a cAMP dependent enhancement of the opening of the Ca2+ channels located on nerve terminals.

Adenylyl Cyclases↗
PubMed2004

Brevetoxin metabolism and elimination in the Eastern oyster (Crassostrea virginica) after controlled exposures to Karenia brevis.

The metabolism and elimination of brevetoxins were examined in the Eastern oyster (Crassostrea virginica) following controlled exposures to Karenia brevis cultures in the laboratory. After a 2-day exposure period ( approximately 62 million cells/oyster), elimination of brevetoxins and their metabolites was monitored by using liquid chromatography/mass spectrometry (LC/MS). Composite toxin in oyster extracts was measured by in vitro assay (i.e. cytotoxicity, receptor binding, and ELISA). Of the parent algal toxins, PbTx-1 and PbTx-2 were not detectable by LC/MS in K. brevis-exposed oysters. PbTx-3 and PbTx-9, which are accumulated directly from K. brevis and through metabolic reduction of PbTx-2 in the oyster, were at levels initially (after exposure) of 0.74 and 0.49 microg equiv./g, respectively, and were eliminated largely within 2 weeks after dosing. PbTx-7 and PbTx-10, the reduced forms of PbTx-1, were non-detectable. Conjugative brevetoxin metabolites identified previously in field-exposed oysters were confirmed in the laboratory-exposed oysters. Cysteine conjugates of PbTx-1 and PbTx-2, and their sulfoxides, were in the highest abundance, as apparent in LC/MS ion traces, and were detectable for up to 6 months after dosing. Composite toxin measurements by in vitro assay also reflected persistence (up to 6 months) of brevetoxin residues in the oyster. Levels of cysteine conjugates, as determined by LC/MS, were well correlated with those of composite toxin, as measured by ELISA, throughout depuration. Composite toxin levels by cytotoxicity assay were well correlated with those by receptor binding assay. Cysteine-PbTx conjugates are useful LC/MS determinants of brevetoxin exposure and potential markers for composite toxin in the Eastern oyster.

Animals↗
PubMed2005

A rapid detection method for paralytic shellfish poisoning toxins by cell bioassay.

We report here a rapid detection method for paralytic shellfish poisoning (PSP) toxins using a cultured neuroblastoma cell line, modified from the bioassay system previously established by Manger et al. [Manger, R.L., Leja, L.S., Lee, S.Y., Hungerford, J.M., Kirkpatrick, M.A., Yasumoto, T., Wekell, M.M., 2003. Detection of paralytic shellfish poison by rapid cell bioassay: antagonism of voltage-gated sodium channel active toxins in vitro. J. AOAC Int. 86 (3), 540-543]. In the present study, we made two major modifications to the previous method. The first is the use of maitotoxin, a marine toxin of ciguatera fish poisoning, which enables the incubation period to be reduced to 6 h when applied to the microplate 15 min prior to the end of the incubation. The second is the use of WST-8, a dehydrogenase detecting water-soluble tetrazolium salt for determining the target cell viability, which permits the omission of a washing step and simplifies the counting process. In addition, we attempted to reduce the required materials as much as possible. Thus, our modified method should be useful for screening the PSP-toxins from shellfish.

Animals↗
PubMed2006

Isolation and identification of pectenotoxins-13 and -14 from Dinophysis acuta in New Zealand.

Two novel pectenotoxins (PTXs), PTX-13 and -14, were isolated from extracts of Dinophysis acuta collected from the west coast of South Island, New Zealand. The compounds were identified as oxidized analogues of PTX-2 by NMR spectroscopic and LC-MS studies. PTX-13 (32R-hydroxyPTX-2) corresponds to the unidentified analogue PTX-11x reported by [Suzuki et al., 2003. Liquid chromatography-mass spectrometry of spiroketal stereoisomers of pectenotoxins and the analysis of novel pectenotoxin isomers in the toxic dinoflagellate Dinophysis acuta from New Zealand. J. Chromatogr. A 992, 141-150]. PTX-13 underwent slow deuteration at the 13beta-position during NMR analysis. PTX-14 corresponds to the 32,36-dehydration product of PTX-13, and may be an artifact.

Animals↗
PubMed2002

Comparison of solid-phase extraction methods for the determination of azaspiracids in shellfish by liquid chromatography-electrospray mass spectrometry.

Azaspiracids have been identified as the cause of a new toxic syndrome called azaspiracid poisoning (AZP) that has led to incidents of human intoxications throughout Europe following the consumption of mussels. Although five AZP toxins have been structurally elucidated to-date, azaspiracid (AZA1), 8-methylazaspiracid (AZA2) and 22-demethylazaspiracid (AZA3) are the predominant toxins. Separation of the three main AZP toxins was achieved using reversed-phase liquid chromatography (LC) and coupled to an electrospray ionisation source of an ion-trap mass spectrometer. Five reversed-phase (C18) and three diol solid-phase extraction (SPE) cartridges were compared for their efficacy in the cleanup of shellfish matrix. The comparison was based on the optimum recoveries of AZA1, AZA2 and AZA3 from extracts of mussel tissues. LC-electrospray MS3 analysis was used to quantify the AZP toxins in wash and eluate fractions in the SPE studies. Good recovery and reproducibility data were obtained for one diol SPE cartridge and two C18 SPE cartridge types.

Chromatography, Liquid↗
PubMed2002

Pectenotoxin-2 seco acid, 7-epi-pectenotoxin-2 seco acid and pectenotoxin-2 in shellfish and plankton from Portugal.

Pectenotoxin-2 seco acid (PTX2sa) and 7-epi-pectenotoxin-2 seco acid (7-epi-PTX2sa) were found in Portuguese shellfish both by fluorescence detection after ADAM derivatisation and, liquid chromatography coupled with mass spectrometry detection. Two time-series both with blue mussel (Mytilus edulis) and common cockle (Cerastoderma edule) from Aveiro lagoon illustrate how PTX2sa has a strong association with Dinophysis acuta occurrence in the plankton, as well as Dinophysis fortii. Data so far excludes D. acuminata from contributing to contamination with pectenotoxins. It also shows that mussel may not be the best indicator of contamination with PTX2sa. At Aveiro lagoon also oyster, razor clam and clams were all less toxic than cockle. Pectenotoxin-2 seco acid was not involved in a previously reported incident of human poisoning that took place in February 1998 after consumption of Donax trunculus. In plankton extracts the most abundant pectenotoxin found was PTX2. Concentration of PTX2sa was around 10% of PTX2, and 7-epi-PTX2sa was not detected.

Animals↗
PubMed2002

Multiple ciguatoxins present in Indian Ocean reef fish.

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.

Animals↗
PubMed2003

Cytochrome c translocation does not lead to caspase activation in maitotoxin-treated SH-SY5Y neuroblastoma cells.

Cytosolic cytochrome c elevation has been associated with activation of caspase-3-like proteases. In this study, we demonstrate that treatment with the neurotoxin and potent calcium channel opener maitotoxin (MTX) induces cytochrome c release from the mitochondria that is not accompanied by caspase activation. Cytochrome c translocation in MTX-treated SH-SY5Y cells was readily apparent after 30 min and peaked at 2.5h. We assayed caspase activity by acetyl-Asp-Glu-Val-Asp-7-amido-4-methylcoumarin (Ac-DEVD-AMC) hydrolysis and by immunoblotting for caspase-3 processing and proteolysis of alphaII-spectrin and PARP. In contrast, treatment with pro-apoptosis agent staurosporine (STS) induced both cytochrome c release and caspase-3 activation after 2h. In addition, with MTX treatment, we found no evidence of caspase activation at any time point or MTX concentration used. Instead, we observed that caspase-9, Apaf-1 and caspase-3 were all partially truncated by calpain under these conditions. These combined effects likely contribute to the lack of caspase activation cascade in MTX-treated cells, despite the presence of cytochrome c in the cytosol.

Caspases↗
PubMed2002

Synthesis of the ABC ring system of Azaspiracid. 2. A systematic study into the effect of C(16) and C(17) substitution on bis-spirocyclization.

[reaction: see text] A systematic study into the effect of C(16) and C(17) substitution on the stereochemical outcome of bis-spirocyclization to form the ABC ring system of azaspiracid is disclosed. Successful construction of the natural 10R,13R bis-spirocyclic stereochemistry has been accomplished on the C(16) benzyloxy-containing precursor.

Alkylation↗
PubMed2005

A convergent coupling strategy for the formation of polycyclic ethers: stereoselective synthesis of the BCDE fragment of brevetoxin A.

A stereoselective synthesis of the BCDE fragment of brevetoxin A has been completed. anti-Glycolate aldol, glycolate alkylation, and ring-closing metathesis reactions were employed as key bond-forming events. A convergent assembly strategy was employed that relied on a Horner-Wadsworth-Emmons union of two complex fragments. Subsequent cyclization and dehydration led to efficient generation of an intermediate endocyclic enol ether, which was advanced to a tetracyclic fragment. [reaction: see text]

Alkylation↗
PubMed2006

Cell growth inhibition and actin cytoskeleton disorganization induced by azaspiracid-1 structure-activity studies.

Azaspiracid-1 (AZA-1) is a marine toxin discovered 10 years ago. Since then, toxicologic studies have demonstrated that AZA-1 targets several organs in vivo, including the intestine, lymphoid tissues, lungs, and nervous system; however, the mechanism of action of AZA-1 remains unknown. Studies in vitro suggest that AZA-1 affects the actin cytoskeleton in nonadherent cells. We characterized the effects of AZA-1 on the cytoskeleton of adherent cells and on cell growth, an adhesion-dependent process in many cell types, and analyzed the structure dependency of this toxicity. Confocal and TIRF imaging of fluorescently labeled cytosketon showed that AZA-1 induced the rearrangement of stress fibers (actin filament bundles) and the loss of focal adhesion points in neuroblastoma and Caco-2 cells, without affecting the amount of polymerized actin. AZA-1 did not seem to alter the microtubule cytoskeleton, but it changed the cell shape and internal morphology observed by phase contrast imaging. Cell growth of lung carcinoma and neuroblastoma cells was inhibited by the toxin, as measured by a sulforhodamine B assay and BrdU incorporation to newly synthesized DNA. Fifteen different fragments and/or stereoisomers of AZA-1 were tested for cytoskeletal rearrangement and cell growth inhibition. Results showed that no fragment or stereoisomer had any activity, except for ABCD-epi-AZA-1, which conserved toxicity. AZA-1-induced reorganization of the actin cytoskeleton concurred with detachment and growth inhibition, three events that are probably related.

Actins↗
PubMedDate not supplied

Effects of brevetoxins on murine myeloma SP2/O cells: aberrant cellular division.

Massive deaths of manatees (Trichechus manatus latirostris) during the red tide seasons have been attributed to brevetoxins produced by the dinoflagellate Karenia brevis (formerly Ptychodiscus breve and Gymnodinium breve). Although these toxins have been found in macrophages and lymphocytes in the lung, liver, and secondary lymphoid tissues of these animals, the molecular mechanisms of brevetoxicosis have not yet been identified. To investigate the effects of brevetoxins on immune cells, a murine myeloma cell line (SP2/O) was used as a model for in vitro studies. By adding brevetoxins to cultures of the SP2/O cells at concentrations ranging from 20 to 600 ng/ml, an apparent increase in proliferation was observed at around 2 hours post challenge as compared to the unchallenged cell cultures. This was followed by a drop in cell number at around 3 hours, suggesting an aberrant effect of brevetoxins on cellular division, the cells generated at 2 hours being apparently short-lived. In situ immunochemical staining of the SP2/O cells at 1 and 2 hour post challenge showed an accumulation of the toxins in the nucleus. A 21-kDa protein was subsequently isolated from the SP2/O cells as having brevetoxin-binding properties, and immunologically identified as p21, a nuclear factor known to down-regulate cellular proliferation through inhibition of cyclin-dependent kinases. These data are the first on a possible effect of brevetoxins on the cell cycle via binding to p21, a phenomenon that needs to be further investigated and validated in normal immune cells.

Animals↗
PubMed1993

Ca(2+)-dependent aggregation of rabbit platelets induced by maitotoxin, a potent marine toxin, isolated from a dinoflagellate.

1. Administration of maitotoxin (MTX), a dinoflagellate toxin, caused aggregation of rabbit washed platelets. The cytosolic Ca2+ concentration ([Ca2+]i), measured by fura-2 fluorescence technique, was also increased by the presence of MTX. Rates of aggregation response and [Ca2+]i-increase were dependent on tested concentrations (3-100 ng ml-1) of the toxin. 2. The MTX-induced platelet aggregation and [Ca2+]i-increase were totally abolished in a Ca(2+)-free solution. The successive administration of Ca2+ in the presence of MTX elicited the aggregation and increase in [Ca2+]i. 3. Ba2+ was capable of substituting for Ca2+ in the MTX-induced platelet aggregation. In the presence of external Ca2+, transition metals, Co2+, Cd2+ and Ni2+, inhibited the aggregation response to MTX. 4. Organic calcium antagonists (verapamil and nifedipine) as well as a cyclo-oxygenase-inhibitor (aspirin) did not apparently inhibit the aggregation response to MTX, except for a high concentration (10(-5) M) of verapamil, while procaine (10 mM) reduced the rate of platelet aggregation. 5. MTX also elicited a release of ATP from platelets, which was abolished in the absence of external Ca2+. 6. In contrast, thrombin 0.5 unit ml-1 could elicit platelet shape change, [Ca2+]i-increase and ATP-release in the absence of external Ca2+. 7. These results suggest that the MTX-induced platelet activation is caused by an enhanced Ca(2+)-influx presumably through voltage-independent Ca2+ channels on the plasma membrane.

Adenosine Triphosphate↗
PubMed1996

Calcium is permeable through a maitotoxin-activated nonselective cation channel in mouse L cells.

The shellfish poison maitotoxin causes the irreversible opening of nonselective cation channels in mouse L cell fibroblasts, consistent with the action of this toxin in other cell types and the previously demonstrated existence of 28-pS voltage-insensitive nonselected cation channels that are activated by platelet-derived growth factor in these cells. Toxin-induced opening of these nonselective cation channels led to increases of intracellular calcium and secondary activation of calcium-activated potassium channel. These effects were completely dependent on influx of extracellular calcium, supporting the conclusion that the maitotoxin-activated nonselective cation channels are permeable to calcium as well as to sodium and potassium. The implication of this finding is that calcium signaling through this channel underlies its links into the growth factor response.

Animals↗