PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Polyether Toxins”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 19 recordsLinked to original sources
PubMed1994

Ionspray mass spectrometry of ciguatoxin-1, maitotoxin-2 and -3, and related marine polyether toxins.

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)

Animals↗
PubMedDate not supplied

Modified immunoassays for polyether toxins: implications of biological matrixes, metabolic states, and epitope recognition.

Polyether marine toxins are responsible for the seafood intoxication phenomena known as neurotoxic shellfish poisoning (due to brevetoxins), ciguatera (due to ciguatoxin), and diarrheic shellfish poisoning (due to okadaic acid). Using traditional techniques of hapten (pure toxin) conjugation to protein to create complete antigen, animal immunization and antibody isolation, and specific antibody subpopulation purification, discriminating antibodies have been isolated that detect brevetoxins and ciguatoxin, but not okadaic acid, in a dose-dependent fashion. Using microorganic chemistry and purified toxins, a unique set of tools has been created for the study of polyether ladder toxin accumulation; depuration; and specific site localization in tissues, food sources, and clinical samples. Developed test protocols can detect toxin in dinoflagellate cells, in extracts from food sources, in seawater and culture media, and in human serum samples. Enzyme-linked immunosorbent assay protocols developed for eventual collaborative testing have been successful in limited applications within the laboratory (correlation coefficient of 0.92 excluding 2 outliers), and alternative formats are being developed to optimize the basic test for use in research laboratories, regulatory laboratories, and field inspections.

Antibodies↗
PubMed1998

Simplified solid-phase membrane immunobead assay (MIA) with monoclonal anti-ciguatoxin antibody (MAb-CTX) for detection of ciguatoxin and related polyether toxins.

The development of a simplified and modified procedure for the assessment of ciguatoxin (CTX) and related polyethers from ciguateric contaminated fish tissues is presented in this study. The previous method, stick-enzyme immunoassay (S-EIA) used an organic correction fluid-coated bamboo paddle stick for the solid phase; this new procedure, membrane immunobead assay (MIA), uses a plastic stick with a synthetic membrane laminated onto one end. The membrane is hydrophobic and serves as the solid-phase receptor for the binding of methanol-extracted CTX or its related polyether lipids from fish tissues. Detection of the bound polyether toxin(s) on the membrane is carried out with colored polystyrene beads coated with monoclonal antibody to CTX (MAb-CTX). Intensity of the color on the membrane is proportional to the amount of toxic polyethers on the membrane. The MIA is compared with previous procedures developed for CTX detection (S-EIA and solid-phase immunobead assay, SPIA) using State of Hawaii Department of Health (DOH) implicated ciguateric fishes, and reef fishes from Hawaii and Kwajalein. The data presented show good correlation between the three test systems, especially with ciguatera implicated fish and toxic, routinely assessed fishes in the mouse toxicity (MT) bioassay. Variations between MT results and those of the S-EIA, SPIA, and MIA of routine fishes are generally attributable to diverse toxins present in the fish species examined. The MIA is a simple, rapid, sensitive, and specific detection method for CTX and its related polyethers, with no reported false negative results. The test is useful for field and personal use and can be adapted to the laboratory for large-scale screening of potentially ciguateric fishes.

Animals↗
PubMed1992

Liquid chromatographic mass spectrometric methods for the determination of marine polyether toxins.

Experiments with novel nitrogenous coumarin-based reagents yielded moderately fluorescent derivatives of brevetoxin-3 and ciguatoxin-1. The diethylaminocoumarin-carbamic acid esters of brevetoxin-3 were resolved by high performance liquid chromatography into two derivative peaks that correspond to substitutions at the C-37 and C-41 hydroxyls. The derivatives produced intense molecular ions under fast atom bombardment ionization conditions, confirming derivative identity. Ciguatoxin-1 was also successfully derivatized, resolved, and identified by HPLC-fluorometry with an estimated lower limit of detection of 0.5 to 1.0 ng.

Chromatography, High Pressure Liquid↗
PubMed1996

Simple Designs for the Construction of Complex Trans-Fused Polyether Toxin Frameworks. A Convergent Strategy Based on Hydroxy Ketone Cyclization of C-Linked Oxacycles.

A single, unified convergent strategy for the stereocontrolled synthesis of trans-fused polyethers was developed. It was demonstrated that the epimerization and reductive intramolecular coupling of hydroxy ketones in reactions with silane-Lewis acids (SI-LA) to generate ethers in C-linked oxacycles is affected by its conformational preference in a predictable manner. The obtained results make evident that the influence of hydrogen bonding between a hemiketal hydroxyl and a 1,3-diaxial C-O bond is regular and predictable and that convergent synthesis of trans-fused polyethers may confidently be conducted on driving ring closure to oxane rings under thermodynamic conditions

Journal Article↗
PubMed1989

Brevetoxins: unique polyether dinoflagellate toxins.

Brevetoxins are lipid-soluble polyether marine toxins of unique structure and pharmacological function. Toxins are active in vivo in the nanomolar to picomolar concentration range and in vitro in isolated neuromuscular or giant axon preparations and in single-cell or subcellular model systems. Their effect is excitatory, mediated by the enhancement of cellular Na+ influx. Brevetoxins bind at site 5 on the voltage-sensitive sodium channel, a specificity shared with ciguatoxin. This site is allosterically linked to other natural toxin binding sites on the channel.

Animals↗
PubMed1996

Microalgal metabolites: a new perspective.

Occurrence of secondary metabolites in microalgae (protoctista) is discussed with respect to the phylogenic or taxonomic relationships of organisms. Biosynthetic mechanisms of certain metabolites such as paralytic shellfish poisoning toxins and polyether toxins are also discussed, and genetic aspects of the secondary metabolite production as well.

Classification↗
PubMed1985

A rapid, simplified enzyme immunoassay stick test for the detection of ciguatoxin and related polyethers from fish tissues.

A simplified and rapid enzyme immunoassay stick test is presented in this study. The salient feature of this test is the use of a coating (Liquid Paper) on the stick to adsorb the lipid ciguatoxin and its related polyether toxins onto the stick. This rapid solid phase stick test has been able to differentiate clinically implicated fishes (14 samples) from non-toxic (60 samples) with P less than 0.005. Comparison of the stick test with the enzyme immunoassay procedure with the positive fish samples demonstrated a good correlation. All samples were positive by both procedures. Further comparison of the stick test, enzyme immunoassay and the mouse bioassay with unknown fish samples showed good relationships between the three procedures. Examination of 71 Seriola dumerili, a fish generally implicated in ciguatera poisoning, with the stick test procedure showed that 89% of the fishes were non-toxic and thus consumed without any incidence of ciguatera poisoning. Analysis of graded concentrations of ciguatoxin, in ng/ml of methanol, showed a typical immunological precipitation pattern. The stick test as conceived is simple and rapid, while retaining its sensitivity and specificity to detect ng levels of ciguatoxin and its related polyether toxins. It is suggested that the stick test will be valuable in the screening of ciguatoxin and related polyether toxins in contaminated fish tissues.

Animals↗
PubMedDate not supplied

Antibodies to maitotoxin elicited by immunization with toxin-fragment conjugates.

Maitotoxin is a water-soluble polyether toxin produced by the benthic dinoflagellate, Gambierdiscus toxicus. Toxin fragments generated by periodate oxidation were conjugated to keyhole limpet hemocyanin, and the resulting immunogens were used to elicit maitotoxin-specific antibodies in mice. A competitive immunoassay developed with polyclonal IgG antibodies detected approximately 3 nM purified maitotoxin standard (IC50 approximately 13 nM; 45 ng/ml) but did not detect other polyether marine toxins. These are the first reported maitotoxin-specific antibodies.

Animals↗
PubMed2001

The red tide toxin, brevetoxin, induces embryo toxicity and developmental abnormalities.

Brevetoxins are lipophilic polyether toxins produced by the red tide dinoflagellate Gymnodinium breve, and their neurotoxic effects on adult animals have been documented. In this study, we characterized adverse developmental effects of brevetoxin-1 (PbTx-1) using an exposure paradigm that parallels the maternal oocyte transfer of toxin. Medaka fish (Oryzias latipes) embryos were exposed to PbTx-1 via microinjection of toxin reconstituted in a triolein oil droplet. Embryos microinjected with doses of 0.1-8.0 ng/egg (ppm) of brevetoxin-1 exhibited pronounced muscular activity (hyperkinesis) after embryonic day 4. Upon hatching, morphologic abnormalities were commonly found in embryos at the following lowest adverse effect levels: 1.0-3.0 ppm, lateral curvature of the spinal column; 3.1-3.4 ppm, herniation of brain meninges through defects in the skull; and 3.4-4.0 ppm, malpositioned eye. Hatching abnormalities were also commonly observed at brevetoxin doses of 2.0 ppm and higher with head-first, as opposed to the normal tail-first, hatching, and doses > 4.1 ng/egg produced embryos that developed but failed to hatch. Given the similarity of developmental processes found between higher and lower vertebrates, teratogenic effects of brevetoxins have the potential to occur among different phylogenetic classes. The observation of developmental abnormalities after PbTx-1 exposure identifies a new spectrum of adverse effects that may be expected to occur following exposure to G. breve red tide events.

Animals↗
PubMed2001

Polyclonal and monoclonal antibodies to PbTx-2-type brevetoxins using minute amount of hapten-protein conjugates obtained in a reversed micellar medium.

Minute amount of Brevetoxin PbTx-3 (400 microg; 0.446 micromol) was converted into an hemisuccinate derivative (PbTx-3 HS) then covalently linked to bovine serum albumin (BSA) and ovalbumin (OVA) in a reversed micellar medium. According to the efficient cyclic synthetic procedure described, the epitope density of the conjugates was around 10 and 20 for OVA and BSA carriers, respectively. The kinetics of antibody production in sequential sera harvested from a single BALB/c mouse immunised by multiple intraperitoneal (i.p.) injections of PbTx-3-BSA conjugate was performed by enzyme-linked immunosorbent assay (ELISA). Two monoclonal antibodies (MAbs) against PbTx-3 were selected from fusion of the mouse immune splenocytes with the P3-X63-Ag 8.653 myeloma cells. In competitive inhibition ELISA experiments, both polyclonal antibodies and MAbs exhibited strong cross-reactivity (> or = 100%) to other PbTx-2-type toxins (PbTx-2 and -9) but low or moderate cross-reactivity (6-15%) to a PbTx-1-type toxin (PbTx-1). Moreover, using these two MAbs, a low cross-reactivity with okadaic acid (3%) was noticed but no significant cross-reactivity was observed with two ciguatoxins (CTX-1B and CTX-3C) over the concentration range studied. The apparent dissociation constant (K(D)) for the interaction of these MAbs with free PbTx-2-type toxins was in the 10(-6)-10(-7)M range. The performance of this MAb-based assay (limit of detection approximately 5ng/well; working range=8-150ng/well) coupled with adequate extraction methods would provide an alternative assay to the mouse i.p. bioassay for routine shellfish monitoring. This production and characterisation of MAbs using small amount of polyether toxins in a reversed micellar medium appear most valuable for the development of immunoassays to other highly potent but poorly available marine polyether toxins like ciguatoxins (CTXs).

Animals↗
PubMed1992

Rapid facile solid-phase immunobead assay for screening ciguatoxic fish in the market place.

The precision of the solid-phase immunobead assay (Ciguatect) to detect toxins associated with ciguatera poisoning have been evaluated through analysis of toxic and non-toxic fish obtained from fishing areas around the Hawaiian Islands. The Ciguatect test kit has been optimized for application to field/marketplace screening of ciguatoxic fish. Twelve parrot, surgeon, and amberjack fish fillet and fish extract test portions containing various concentrations of toxins were distributed to participating laboratories for analysis. The presence or absence of ciguatera-related toxins is determined by binding the toxins to a membrane attached to a plastic strip and exposing the toxin ladened membrane to a monoclonal antibody-colored latex bead complex which has a high specificity for ciguatera-related toxins. The intensity of the color on the membrane denotes the presence of the toxins in the fish or fish extract. Toxic components in the fish were confirmed by extraction, column purification, and toxicity testing using the brine shrimp (Artemia sp.) assay. Okadaic acid was used to standardize both the S-PIA and brine shrimp assays. For determination of ciguatoxin and related polyether toxins in parrot, surgeon, and amberjack fish fillets, the relative standard deviations for repeatability (RSDR) were 13.5, 9.0 and 4.3%, respectively, and the relative standard deviations for reproducibility (RSDR) were 44.4, 29.7 and 14.3%, respectively, for concentrations ranging from 1-4 ng/test strip. For determination of ciguatoxin and related polyether toxins in parrot, surgeon, and amberjack fish extracts, the RSDR were 5.8, 4.8, and 3.7%, respectively, and the RSDR were 11.9, 9.9, and 7.6%, respectively, for concentrations ranging from 3-5 ng/test strip.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMedDate not supplied

Effect of maitotoxin on guanine nucleotide interaction with G-protein alpha subunits.

Maitotoxin is a potent water-soluble polyether toxin produced by the marine dinofiagellate Gambierdiscus toxicus. Although associated with increased calcium uptake, mobilization of internal calcium stores, and enhanced phosphoinositide metabolism, the primary molecular mechanism underlying its actions remains unclear. In this study, we evaluated the effects of maitotoxin (MTX) on the interaction of guanine nucleotides with G-protein alpha subunits. Equilibrium binding of the nonhydrolyzable GTP analog, GTPgammaS, to alpha subunits (Go, Gs, Gi1, Gi2, and Gi3) was decreased in the presence of MTX. Furthermore, reconstitution of Galpha with Gbetagamma dimer showed a reversal of the inhibition elicited by MTX. GDP/GTP exchange rate for Galpha subunits was significantly inhibited in the presence of MTX. MTX had no effect on the rate of GDP or GTP dissociation from alpha subunits. Also, the mastoparan-induced component of nucleotide exchange is not effected by MTX. These results suggest that MTX acts on Galpha subunits to modulate their interaction with guanine nucleotides, perhaps by stabilizing an empty state of the alpha subunit. Accordingly, MTX may disrupt the normal signal transduction pathways by inhibiting GTP binding to Galpha subunits and interfering with the GDP/GTP exchange.

Animals↗
PubMed1998

Behavioral thermoregulatory response to maitotoxin in mice.

Many types of marine algal toxins induce marked hypothermic responses in mice. However, it is not known if the thermoregulatory response to these toxins results from dysfunction in the control of core temperature (Tc) or is a coordinated response to lower Tc as occurs with a variety of xenobiotic insults. Female CD-1 mice were administered purified maitotoxin (338 ng/kg; IP) and placed in a temperature gradient for 5 h that permitted the selection of ambient temperatures (Ta) ranging between 15 and 37 degrees C. Tc was monitored simultaneously by radiotelemetric probes that were surgically implanted into the abdominal cavity at least one week before maitotoxin injection. Maitotoxin led to a rapid reduction in Tc from 37 to 34 degrees C within 30 min after injection. There was a simultaneous 4 degrees C reduction in Ta selected by mice within 15 min after injection. Selected Ta recovered rapidly, increased above baseline for approximately one hour, then remained near baseline levels for the remainder of the test period in the gradient. Tc remained approximately 1 to 2 degrees C below control levels throughout the test period. In the temperature gradient, mice can select Ta's warm enough to offset the hypothermic effects of maitotoxin. That cooler Ta's are selected initially after maitotoxin injection suggest that the central neural control of body temperature is affected by the toxin. We postulate that the hypothermic response may represent an adaptive response to enhance survival following exposure to polyether toxins.

Adaptation, Physiological↗
PubMed1997

[Determination of phycotoxins in aquatic medium by capillary electrophoresis].

Marine phycotoxins present a major public health problem due to their ability to contaminate seafoods. Toxic phytoplankton is not limited, however, to the coastal areas in Europe. There are more and more problems in freshwater reservoirs, in lakes, and in ponds from which grazing animals get their water. Okadaic acid (OA), a polyether toxin from the marine dinoflagellate, Prorocentrum lima, and microcystins (MCYSTs), a potent hepatotoxic cyclic heptapeptides produced by many strains of cyanobacteria have been shown to be a powerful tumor promotor. Thus, considerable effort has been undertaken to find sensitive and easy detection techniques for the determination of phycotoxins from various matrices (microalgae, freshwater, mussels, fish, ...). Different biological and chemical methods have been developed to identify these toxins in shellfish and fish. The mouse bioassay method has been widely used for the detection of toxins such as maitotoxin and ciguatoxin, which are not easily identified by chemical procedures. In this report we describe a capillary electrophoretic method that enables us to detect okadaic acid, microcystins (MCYST-YR, MCYST-LR, MCYST-RR) and maitotoxin in picogram range.

Animals↗
PubMed1999

Heavy metals, lipid peroxidation, and ciguatera toxicity in the liver of the Caribbean barracuda (Sphyraena barracuda).

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.

Animals↗