Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “Polyether Toxins”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

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

At least 109 records · Page 6Linked to original sources
PubMed2005

Brevetoxicosis: red tides and marine mammal mortalities.

Potent marine neurotoxins known as brevetoxins are produced by the 'red tide' dinoflagellate Karenia brevis. They kill large numbers of fish and cause illness in humans who ingest toxic filter-feeding shellfish or inhale toxic aerosols. The toxins are also suspected of having been involved in events in which many manatees and dolphins died, but this has usually not been verified owing to limited confirmation of toxin exposure, unexplained intoxication mechanisms and complicating pathologies. Here we show that fish and seagrass can accumulate high concentrations of brevetoxins and that these have acted as toxin vectors during recent deaths of dolphins and manatees, respectively. Our results challenge claims that the deleterious effects of a brevetoxin on fish (ichthyotoxicity) preclude its accumulation in live fish, and they reveal a new vector mechanism for brevetoxin spread through food webs that poses a threat to upper trophic levels.

Animals↗
PubMed2005

Effects of inhaled brevetoxins in allergic airways: toxin-allergen interactions and pharmacologic intervention.

During a Florida red tide, brevetoxins produced by the dinoflagellate Karenia brevis become aerosolized and cause airway symptoms in humans, especially in those with pre-existing airway disease (e.g., asthma). To understand these toxin-induced airway effects, we used sheep with airway hypersensitivity to Ascaris suum antigen as a surrogate for asthmatic patients and studied changes in pulmonary airflow resistance (R(L) after inhalation challenge with lysed cultures of K. brevis (crude brevetoxins). Studies were done without and with clinically available drugs to determine which might prevent/reverse these effects. Crude brevetoxins (20 breaths at 100 pg/mL; n = 5) increased R(L) 128 +/- 6% (mean +/- SE) over baseline. This bronchoconstriction was significantly reduced (% inhibition) after pretreatment with the glucocorticosteroid budesonide (49%), the beta(2) adrenergic agent albuterol (71%), the anticholinergic agent atropine (58%), and the histamine H1-antagonist diphenhydramine (47%). The protection afforded by atropine and diphenhydramine suggests that both cholinergic (vagal) and H1-mediated pathways contribute to the bronchoconstriction. The response to cutaneous toxin injection was also histamine mediated. Thus, the airway and skin data support the hypothesis that toxin activates mast cells in vivo. Albuterol given immediately after toxin challenge rapidly reversed the bronchoconstriction. Toxin inhalation increased airway kinins, and the response to inhaled toxin was enhanced after allergen challenge. Both factors could contribute to the increased sensitivity of asthmatic patients to toxin exposure. We conclude that K. brevis aerosols are potent airway constrictors. Clinically available drugs may be used to prevent or provide therapeutic relief for affected individuals.

Airway Resistance↗
PubMed1996

Study on neurotoxic shellfish poisoning involving the oyster, Crassostrea gigas, in New Zealand.

Lipid-soluble polyether marine toxins were isolated from 80% methanol extract of oysters, Crassostrea gigas, harvested in 1993 at Tiki Road, Coromandel Peninsula, New Zealand, by chromatography on columns of LH-20 and ODS (C18), followed by reversed-phase high-performance liquid chromatography. They were identified as known brevetoxins, PbTx-2 and 3. PbTx-3 was also isolated from oysters collected at Rangaunu Harbour in February 1994 and June 1995, followed by the above procedures.

Animals↗
PubMed1995

The relationship of brevetoxin 'length' and A-ring functionality to binding and activity in neuronal sodium channels.

BACKGROUND: Brevetoxins are polyether ladder toxins that are ichthyotoxic at nanomolar concentrations. They bind to voltage-gated sodium channels, causing four distinct electrophysiological effects: (i) a shift of activation potential; (ii) occurrence of subconductance states; (iii) induction of longer mean open times of the channel; and (iv) inhibition of channel inactivation. We set out to determine whether these functions all require the same structural elements within the brevetoxin molecules. RESULTS: Several synthetically prepared structural analogs of brevetoxin B were examined in synaptosome receptor binding assays and by functional electrophysiological measurements. A truncated analog is not ichthyotoxic at micromolar concentrations, shows decreased receptor-binding affinity, and causes only a shift of activation potential without affecting mean open times or channel inactivation. An analog with the A-ring carbonyl removed binds to the receptor with nanomolar affinity, produces a shift of activation potential and inhibits inactivation, but does not induce longer mean open times. An analog in which the A-ring diol is reduced shows low binding affinity, yet populates five subconductance states. CONCLUSIONS: Our data are consistent with the hypothesis that binding to sodium channels requires an elongated cigar-shaped molecule, approximately 30 A long. The four electrophysiological effects of the brevetoxins are not produced by a single structural feature, however, since they can be decoupled by using modified ligands, which are shown here to be partial sodium channel agonists. We propose a detailed model for the binding of brevetoxins to the channel which explains the differences in the effects of the brevetoxin analogs. These studies also offer the potential for developing brevetoxin antagonists.

Animals↗
PubMed1999

Fluorometric analysis of pectenotoxin-2 in microalgal samples by high performance liquid chromatography.

A rapid HPLC method with fluorescence detection of pectenotoxin-2 (PTX2), a polyether macrolide toxin, in microalgae is presented. A dienophile reagent, DMEQ-TAD, was used for precolumn fluorescence labeling. PTX2 could be quantitatively detected in the range 1-200 ng. This method confirmed the occurrence of PTX2 in net haul samples mostly composed of dinoflagellates Dinophysisspp. collected in the Adriatic Sea, Italy and Mutsu Bay, Japan.

Animals↗
PubMed1999

Mechanisms underlying the hemolytic and ichthyotoxic activities of maitotoxin.

Maitotoxin (MTX), a putative Ca(2+) channel activator produced by the dinoflagellate Gambierdiscus toxicus showed extremely potent hemolytic and ichthyotoxic activities. Hemolysis of 1% mouse blood cell suspension in saline occurred at 15 nM of MTX. The activity was enhanced six-fold in the presence of 10 microM of Ca(2+) and completely blocked by EDTA2Na, indicating its dependency on external Ca(2+). The MTX-induced hemolysis was little affected by L-type Ca(2+) channel blockers (diltiazem, nifedipine, verapamil) but was strongly inhibited by calmodulin blockers (prenylamine and chlorpromazine) or a phospholipase A2 inhibitor (quinacrine). MTX was mimicked by a calcium ionophore, calcimycin. Based on these results, a series of cellular events triggered by MTX were presumed to occur in the following sequence: increased Ca(2+) entry in cells, activation of calmodulin, promotion of phospholipase A2 activity, and finally destruction of cell membrane resulting from hydrolysis of membrane lipids. The sensitivity of blood cells to MTX varied significantly, dependent on the animal sources. Nucleated blood cells of carps and chickens were 100 times more resistant than those of mammals. LC(50) of MTX to freshwater fish Tanichthys albonubes in Ca(2+) free media (pH 8) was 5 nM but was markedly lowered to 3 pM by raising pH to 8 and increasing Ca(2+) concentration to 2 mM. In a marine environment MTX was 2000 times more toxic to fish than 42-di-hydrobrevetoxin-B (PbTx-3), one of the best known ichthyotoxins of red-tide origins.

3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethy↗
PubMed1995

Maitotoxin-elicited calcium influx in cultured cells. Effect of calcium-channel blockers.

Maitotoxin elicited a marked influx of 45Ca2+ into NIH 3T3 fibroblast cells. The influx was blocked by imidazoles (econazole, miconazole, SKF 96365, clotrimazole, calmidazolium) with IC50 values from 0.56 to 3 microM. Phenylalkylamines (verapamil, methoxyverapamil) and nitrendipine were less potent, and diltiazem was very weak. Among other calcium blockers, the diphenylbutylpiperidines fluspirilene and penfluridol, the diphenylpropylpiperidine loperamide, and the local anesthetic proadifen were quite active with IC50 values of 2-4 microM. The pattern of inhibition of maitotoxin-elicited calcium influx did not correspond to the ability of the agents to block elevation of calcium that ensues through calcium-release activated calcium (CRAC) channels after activation of phosphoinositide breakdown by ATP in HL-60 cells. The imidazoles did block CRAC channels, but fluspirilene, penfluridol, loperamide and proadifen were ineffective. Loperamide actually appeared to enhance influx of calcium via the activated CRAC channels. The imidazoles, in particular calmidazolium, caused an apparent influx of calcium and caused a stimulation of phosphoinositide breakdown in HL-60 cells.

3T3 Cells↗
PubMed1985

Ca-dependent arrhythmogenic effects of maitotoxin, the most potent marine toxin known, on isolated rat cardiac muscle cells.

Maitotoxin (MTX) (0.1-10 ng/ml) caused an increase in the degree and the rate of contraction and subsequent arrhythmogenic actions in rat myocardial cells. These effects of MTX were inhibited by verapamil and were abolished by Ca2+-free medium. The MTX-induced effects on cardiac myocytes were enhanced by increasing the Ca2+ concentration. These results suggest that MTX elevates the permeability of cardiac muscle membrane to Ca2+ to increase the intracellular Ca2+ concentration, and thus induces excitatory effects.

Animals↗
PubMed1996

Na(+)-permeable channels induced by maitotoxin in guinea-pig single ventricular cells.

The characteristics of maitotoxin-induced single channel currents were studied in guinea-pig single ventricular cells using the cell-attached or inside-out configuration of the patch clamp. When the patch electrode was filled with normal Tyrode solution containing 10 nM maitotoxin, elementary currents flowing through the single channel were observed in the cell-attached patch. The amplitude of the single channel current at the resting potential was 1.6 +/- 0.1 pA. The current-voltage relation of the current was linear and the single channel conductance was 16.0 +/- 0.9 pS. The distribution of open times was fitted by a single exponential function (decay time constant: 27 ms), while that of closed times was fitted by the sum of two exponential functions (decay time constants: 1.6 and 34 ms). When the electrode solution was filled with the Ca(2+)-free Tyrode solution, maitotoxin also induced single channel currents with parameters similar to those in the normal Tyrode solution. Under inside-out patch clamp conditions and in 150 mM Na+ solution on both sides of the patch membrane, maitotoxin also induced single channel currents. Choline+ could not substitute for Na+. These results indicate that maitotoxin induces single ionic channels irrespective of the presence or absence of Ca2+ and that the charge carrier of the single channel current is Na+ rather than Ca2+. The increase in Na+ permeability through maitotoxin-induced channels may be possibly responsible for its biological actions.

Animals↗
PubMed1989

Maitotoxin-induced liver cell death involving loss of cell ATP following influx of calcium.

Maitotoxin, one of the most potent marine toxins known, produced cell death in cultures of rat hepatocytes with a TD50 of 80 pM at 24 hr. The cell death, as indicated by a dose- and time-dependent leakage of lactate dehydrogenase (LDH), was also associated with the leakage of [14C]adenine nucleotides from hepatocytes prelabeled with [14C]-adenine. The toxic effect of maitotoxin was completely abolished by the omission of calcium from the culture medium. The cell death induced by maitotoxin increased with increasing concentrations of calcium in the medium. Treatment of hepatocytes with low concentrations of the toxin (less than 0.5 ng/ml) resulted in increases in 45Ca influx into the cells. At higher concentrations of maitotoxin (greater than 1ng/ml), the initial increase in 45Ca influx was followed by the release of the 45Ca from the cells into the medium. Since the 45Ca release paralleled the LDH leakage, the release of calcium was due to cell death. The 45Ca influx, [14C]adenine nucleotide leakage, and LDH leakage were effectively inhibited by verapamil, a calcium channel blocker. Maitotoxin also induced a time- and dose-dependent loss of ATP from hepatocytes, which preceded the [14C]adenine nucleotide and LDH leakage. Thus, it appears that the cell death resulting from maitotoxin treatment is caused by the elevated intracellular calcium, which in turn inhibits mitochondrial oxidative phosphorylation causing depletion of cell ATP. Loss of cell ATP may be the causative event in the maitotoxin-induced cell death.

Adenosine Triphosphate↗
PubMed1982

Studies on the mode of action of ciguateric toxins.

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.

Adrenalectomy↗
PubMed1992

Antibodies to brevetoxin B: serologic differentiation of brevetoxin B and brevetoxin A.

A brevetoxin B immunogen was prepared by reacting brevetoxin B with the amino groups of bovine albumin followed by treatment with sodium borohydride. Immunized rabbits produced antibodies that bound [3H]brevetoxin B-alcohol. This binding increased with repeated immunization (KD for one rabbit after three courses of immunization was about 10 pM). Brevetoxin B inhibited greater than 500 times more effectively than brevetoxin A. When tested in a competitive binding assay with [3H]brevetoxin B-alcohol-brevetoxin B antibody, the alcohol was six times more effective as an inhibitor than brevetoxin B. Despite some similarities in structure with brevetoxin A, the antibodies to brevetoxin B did not recognize the backbone of brevetoxin A.

Animals↗
PubMed1994

Brevetoxin: tissue distribution and effect on cytochrome P450 enzymes in fish.

As part of our investigation of the metabolism of brevetoxin (PbTx) in fish, we initiated a two-part study to determine the toxin's tissue distribution and its ability to induce xenobiotic metabolizing enzymes. In the first study, gulf toadfish (Opsanus beta) were administered 14C-PbTx-3 orally in a fishmeal slurry and sacrificed 72 hr later. Radioactivity was greatest in the hepatobiliary system (40% of body burden), representing the key role this system plays in the detoxification and elimination of brevetoxin. Muscle tissue contained 27%, followed by gastrointestinal tract (25%). To investigate the effects of PbTx on xenobiotic metabolizing enzymes, immature redfish (Scianops ocellatus) were given two doses of brevetoxin (1.5 or 2.5 micrograms/100 g body weight) or cod liver oil in a fishmeal slurry by gavage. The activities of two hepatic P450 enzymes, ethoxyresorufin O-deethylase (EROD) and pentoxyresorufin O-depentylase (PROD), as well as the cytosolic enzyme, glutathione S-transferase (GST), were measured. At the higher dose, PbTx significantly increased EROD activity. These results suggest that brevetoxin is capable of inducing an important xenobiotic metabolizing enzyme (EROD).

Animals↗
PubMed1994

Brevetoxin PbTx-2 immunology: differential epitope recognition by antibodies from two goats.

The epitopic regions of the brevetoxin PbTx-3 molecule, produced by the marine dinoflagellate Ptychodiscus brevis, have been identified by structural modification at three distinct regions of the toxin. These are: the A-ring lactone region of the molecule, the K-ring side-chain and the H-ring. The modified PbTx-3 derivatives were tested for their ability to bind brevetoxin goat antisera directed against the PbTx-3 molecule, by radioimmunoassay. The results showed that at least two major epitopes and one minor epitope are recognized: the A-ring lactone region of the molecule and the K-ring side-chain, and the H-ring. The results illustrate the variety of antibodies which may be produced, even within a species, and suggests that epitope characterization is important in the development of assays which are to be employed in seafood safety issues.

Animals↗
PubMed2004

Confirmation of brevetoxin metabolism in cockle, Austrovenus stutchburyi, and greenshell mussel, Perna canaliculus, associated with New Zealand neurotoxic shellfish poisoning, by controlled exposure to Karenia brevis culture.

We examined metabolism of PbTxs in New Zealand cockle, Austrovenus (A.) stutchburyi, and greenshell mussel, Perna (P.) canaliculus, by means of liquid chromatography coupled with tandem mass spectrometry. PbTx-2, PbTx-3 and BTX-B5 were detected in Karenia (K.) brevis culture medium in the ratio of ca. 50:2:5. The amounts of PbTx-3 and BTX-B5 were greatly increased in both seawater and shellfish exposed to K. brevis cultures or supernatant prepared by disruption of K. brevis under appropriate condition, while those of PbTx-2 were decreased. Some PbTx-2 was present in P. canaliculus, but not in A. stutchburyi. Low levels of BTX-B1 were detected in A. stutchburyi, but not P. canaliculus. Levels of PbTx-3 and BTX-B5 were highest immediately after exposure and then declined rapidly in both shellfish. BTX-B1 increased in concentration after exposure, and was then gradually eliminated from A. stutchburyi. Three successive exposures of A. stutchburyi to K. brevis cultures resulted in similar initial levels of PbTx-3 and BTX-B5, while BTX-B1 accumulated after each dose. In P. canaliculus, initial levels of PbTx-3 were similar, while PbTx-2 and BTX-B5 accumulated after each dose. PbTx-3 and BTX-B5 are proposed to be suitable markers for monitoring shellfish toxicity after a red tide event.

Animals↗
PubMed2006

Effects of the dinoflagellate Karenia brevis on larval development in three species of bivalve mollusc from Florida.

The effects of Karenia brevis (Wilson clone) on larval survival and development of the northern quahog, Mercenaria mercenaria, eastern oyster, Crassostrea virginica and bay scallop, Argopecten irradians, were studied in the laboratory. Larvae were exposed to cultures of whole and lysed cells, with mean total brevetoxin concentrations of 53.8 and 68.9 microgL(-1), respectively. Survival of early (3-day-old) larvae was generally over 85% for all shellfish species at K. brevis densities of 100 cells ml(-1) or less, and not significantly different between whole and lysed culture. At 1000 cells ml(-1), survival was significantly less in lysed culture than whole culture for both M. mercenaria and C. virginica. Survival of late (7-day-old) larvae in all three species was not significantly affected by K. brevis densities of 1000 cells ml(-1) or less. At 5000 cells ml(-1), however, survival was reduced to 37%, 26% and 19% for A. irradians, M. mercenaria and C. virginica, respectively. Development of C. virginica and M. mercenaria larvae was protracted at K. brevis densities of 1000 cells ml(-1). These results suggest that blooms of K. brevis, and particularly their associated brevetoxins, may have detrimental consequences for Florida's shellfisheries by disrupting critical larval processes. Special attention should be paid to blooms of K. brevis where these shellfish occur naturally or where aquaculture and restoration activities are either ongoing or planned.

Animals↗