Carmen Vale

University of Santiago de Compostela | USC

Paralytic shellfish poisoning is a foodborne illness that typically derive from the consumption of shellfish contaminated with saxitoxin-group of toxins produced by dinoflagellates of the genus Gymnodinium, Alexandrium and Pyrodinium. N-sulfocarbamoyl, carbamate and dicarbamoyl are the most abundant. In 2007 and 2008 some episodes of PSP occurred i...

Emerging marine biotoxins such as ciguatoxins and brevetoxins have been widely and independently studied as food pollutants. Their maximum levels in food components were set without considering their possible synergistic effects as consequence of their coexistence in seafood and their action at the same cellular target. The absolute lack of data an...

The growing concern about ciguatera fish poisoning (CF) due to the expansion of the microorganisms producing ciguatoxins (CTXs) increased the need to develop a reliable and fast method for ciguatoxin detection to guarantee food safety. Cytotoxicity assay on the N2a cells sensitized with ouabain (O) and veratridine (V) is routinely used in ciguatoxi...

Emerging marine biotoxins such as ciguatoxins and pyrethroid compounds, widely used in agriculture, are independently treated as environmental toxicants. Their maximum residue levels in food components are set without considering their possible synergistic effects as consequence of their interaction with the same cellular target. There is an absolu...

Ciguatoxins (CTX) cause ciguatera poisoning, which is the most common reported human food poisoning related to natural marine toxins. Pacific ciguatoxins are the most abundant and studied CTX analogues; however, the growing distribution of Caribbean analogues and the limited data available on their biological effects make necessary to re-evaluate t...

Okadaic acid (OA) is an important marine lipophilic phycotoxin responsible for diarrhetic shellfish poisoning (DSP). This toxin inhibits protein phosphatases (PPs) like PP2A and PP1, though, this action does not explain OA-induced toxicity and symptoms. Intestinal epithelia comprise the defence barrier against external agents where transport of flu...

Ciguatoxins are marine compounds that share a ladder-shaped polyether structure produced by dinoflagellates of the genus Gambierdiscus and Fukuyoa, and include maitotoxins (MTX1 and MTX3), ciguatoxins (CTX3C) and analogues (gambierone), components of one of the most frequent human foodborne illness diseases known as ciguatera fish poisoning. This d...

Ciguatoxins (CTX) cause ciguatera fish poisoning, which is the most common reported hu-man food poisoning related to natural marine toxins. Pacific ciguatoxins are the most abundant and studied CTX analogues, however, the growing distribution of Caribbean analogues and the limited data available on their biological effects makes necessary to re-eva...

Marine phycotoxins are a multiplicity of bioactive compounds which are produced by microalgae and bioaccumulate in the marine food web. Phycotoxins affect the ecosystem, pose a threat to human health, and have important economic effects on aquaculture and tourism worldwide. However, human health and food safety have been the primary concerns when c...

Ciguatoxins (CTXs) which are produced by dinoflagellates of the genus Gambierdiscus and Fukuyoa and share a ladder-shaped polyether structure, are components of one of the most frequent foodborne illness disease known as ciguatera fish poisoning (CFP). CFP was initially found in tropical and subtropical areas but nowadays the dinoflagellates produc...

The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not f...

Azaspiracids (AZAs) are marine toxins produced by dinoflagellates belonging to the genera Azadinium and Amphidoma that caused human intoxications after consumption of contaminated fishery products, such as mussels. However, the exact mechanism for the AZA induced cytotoxic and neurotoxic effects is still unknown. In this study several pharmacologic...

Seafood represents a significant part of the human staple diet. In the recent years, the identification of emerging lipophilic marine toxins has increased, leading to the potential for consumers to be intoxicated by these toxins. In the present work, we investigate the presence of lipophilic marine toxins (both regulated and emerging) in commercial...

Azaspiracid toxins were first identified at the end of the last century in Irish mussels and during the last two decades considerable several cytotoxic and neurotoxic effects caused by these toxins have been described. Azaspiracids are synthesized by dinoflagellates and accumulate in several species of filter-feeding bivalve mollusks, therefore inc...

Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs,...

Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the r...

Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na+/K+-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several repo...

Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. InitiallyTTX was associated with human food intoxications in Japan, but nowadays, concerns about thehuman health risks posed by TTX have increased in Europe after the identification of the toxin infish, marine gastropods, and bivalves captured in European waters. Even whe...

Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described...

Ciguatoxins are polyether marine toxins that act as sodium channel activators. These toxins cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents several symptoms in humans including long-term neurological alterations. Earlier work has shown that both acute and chronic exposure of primary cortical neurons...

Maitotoxins (MTX) are among the most potent marine toxins identified to date causing cell death trough massive calcium influx. However, the exact mechanism for the MTX-induced calcium entry and cytotoxicity is still unknown. In this work, the effect of MTX-1 on the cytosolic free calcium concentration and cellular viability of human neuronal stem c...

Spirolides are marine toxins, produced by dinoflagellates that act as potent antagonists of nicotinic acetylcholine receptors. These compounds are not toxic for humans and since there are no reports of human intoxications caused by this group of toxins they are not yet currently regulated in Europe. Currently 13-desmethyl spirolide C, 13,19-didesme...

Since the acceptation of analytical methods, especially chromatographic separation with mass spectrometric detection, for the control of marine toxins in seafood, virtually all toxins are covered by an analytical control, with the exception of saxitoxin and analogs. Saxitoxins are monitored by means of a mouse bioassay or by using a fluorescent met...

The first in vitro system for the culture of primary neurons was developed in 1977. Since then, the culture systems for hippocampal and cortical neurons, as well as neuron cell lines, have improved dramatically. Primary neuronal cultures provide a defined environment where neurons can be studied in isolation from other cell types and are a powerful...

Ciguatera is a human global disease caused by the consumption of contaminated fish that have accumulated the sodium channel activator toxins ciguatoxins (CTX). Symptoms of ciguatera include neurological alterations such as paraesthesiae, dysaesthesiae, depression and heightened nociperception, among others. An important issue to understand these lo...

Ciguatoxins are sodium channels activators that cause ciguatera, one of the most widespread nonbacterial forms of food poisoning, which presents with long term neurological alterations. In central neurons, chronic perturbations in activity induce homeostatic synaptic mechanisms that adjust the strength of excitatory synapses and modulate glutamate...

Ciguatera is a global human disease caused by the consumption of contaminated fish that have accumulated the sodium channel activator toxins known as ciguatoxins. These toxins activate the opening of voltage-dependent sodium channels at hyperpolarizing membrane potentials, producing cell membrane depolarization at rest, mainly by increasing sodium...

Filamentous cyanobacteria of the genus Phormidium have been rarely studied for their chemical diversity. For the first time, the cultivable Phormidium autumnale was shown to produce a prenylated cyclic peptide named autumnalamide (1). The structure of this peptide was fully determined after a deep exploration of the spectroscopic data, including NM...

Gambierol is a marine polycyclic ether toxin, produced along with ciguatoxin congeners by the dinoflagellate Gambierdiscus toxicus. We have recently reported that two truncated skeletal analogs of gambierol comprising the EFGH- and BCDEFGH-rings of the parent compound showed similar potency to gambierol on voltage-gated potassium channels (Kv) inhi...

INTRODUCTION Crambescins and crambescidins are guanidine alkaloids first reported in the early 90s. They are produced by the red encrusting marine sponge Crambe crambe widely distributed in the Western Mediterranean Sea but also in the Macaronesian archipelagos (Berlinck et al., 1990;Berlinck et al., 1993). There are few studies about the biologic...

Ciguatoxins (CTXs) and maitotoxins (MTXs) are polyether ladder shaped toxins derived from the dinoflagellate Gambierdiscus toxicus. Despite 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 ef...

Azaspiracids and yessotoxins (YTX) are marine toxins that still pose a scientific problem with regard to their mechanism of action. Azaspiracids are toxins that were linked to anionic channels, hERK potassium channels, c-Jun-N-terminal protein kinase kinases, adhesion proteins, and calcium pools. Their mechanism of action, although unknown, causes...

Yessotoxin is a marine phycotoxin that induces motor alterations in mice after intraperitoneal injection. In primary cortical neurons Yessotoxin treatment induced a caspase-independent cell death with an IC50 of 4.27 nM. This neurotoxicity was enhanced by 4, 4'-Diisothiocyanatostilbene-2, 2'-disulfonic acid and partially blocked by amiloride. Unlik...

Spirolides are marine toxins that are not currently in the routine monitoring assays. Nicotinic receptors seem to be the target of these compounds making them a promising pharmacological tool for related diseases as dementias as previously shown in vitro. In the present work, the bioavailability of 13-desMethyl spirolide C (13-desMeC) in the brain...

Crambescins and crambescidins are two families of guanidine alkaloids from the marine sponge Crambe Crambe. It is known that crambescidin 816 (Cramb816) blocks calcium channels in a neuroblastoma X glioma cell line. Since ion channels are frequent targets for natural toxins, we examined the effect of Cramb816 and three compounds from the crambescin...

Spirolides are marine toxins that are not currently in the routine monitoring assays. Nicotinic receptors seem to be the target of these compounds making them a promising pharmacological tool for related diseases as dementias as previously shown in vitro. In the present work, the bioavailability of 13-desMethyl spirolide C (13-desMeC) in the brain...

The polycyclic ether class of marine natural products has attracted the attention of researchers due to their complex and large chemical structures and diverse biological activities. Gambierol is a marine polycyclic ether toxin, first isolated along with ciguatoxin congeners from the dinoflagellate Gambierdiscus toxicus. The parent compound gambier...

Marine toxins need a continuous monitoring system that is usually implemented in most producer and consumer countries. This is needed to protect consumers, as marine toxins are very toxic compounds. Up to now, the mouse bioassay has been the method of choice, but there is a legal requirement in Europe to replace the bioassay for mass spectrometry w...

Gambierol is a potent neurotoxin that belongs to the family of marine polycyclic ether natural products and primarily targets voltage-gated potassium channels (Kv channels) in excitable membranes. Previous work in the chemistry of marine polycyclic ethers has suggested the critical importance of the full length of polycyclic ether skeleton for pote...

The full chemical reinvestigation of the Mediterranean marine sponge Crambe crambe led to the isolation and structural characterization of 11 crambescin derivatives, including 8 new compounds, together with the known crambescidin 816. HRMS/MS studies allowed the complete assignment of the alkyl chain lengths of these guanidine alkaloids while the a...

Spirolides are marine compounds of the cyclic imine group. Although the mechanism of action is not fully elucidated yet, cholinergic (muscarinic and nicotinic) receptors have been proposed as the main targets of these toxins. In this study we examined the effect of 13-desmethyl spirolide-C (SPX) on amyloid-beta (Aβ) accumulation and tau hyperphosph...

The establishment of toxicity equivalent factors to develop alternative methods to animal bioassays for marine-toxin detection is an urgent need in the field of phycotoxin research. Paralytic shellfish poisoning (PSP) is one of the most severe forms of food poisoning. The toxins responsible for this type of poisoning are highly toxic natural compou...

Gymnodimine (GYM) is a marine phycotoxin with a macrocyclic imine structure, isolated from extracts of the dinoflagellate Karenia selliformis known to act as a cholinergic antagonist with subtype selectivity. However, no data on the chronic effects of this compound has been reported so far. In this work, we evaluated the effect of long term exposur...

Ciguatera is a global disease caused by the consumption of certain warm-water fish (ciguateric fish) that have accumulated orally effective levels of sodium channel activator toxins (ciguatoxins) through the marine food chain. The effect of ciguatoxin standards and contaminated ciguatoxin samples was evaluated by electrophysiological recordings in...

The need to have methods as alternatives to animal bioassays for marine-toxin detection is of paramount importance. Such methods require not only identification of each of the analogs in a phycotoxin group but also the toxicity of each analog. Depending on the nature of the method, not all that have been proposed as potential replacements are equal...

Ciguatera fish poisoning (CFP) is a human foodborne intoxication caused by ingestion of tropical fishes contaminated with the potent polyether toxins known as ciguatoxins (CTXs). These toxins are issued from Gambierdiscus species of dinoflagellates. Herbivorous fish accumulate these toxins in their musculature and viscera after ingesting dinoflagel...

Advances in transgenic technology as well as in the genetics of Alzheimer disease (AD) have allowed the establishment of animal models that reproduce amyloid-beta plaques and neurofibrillary tangles, the main pathological hallmarks of AD. Among these models, 3xTg-AD mice harboring PS1 M146V, APP Swe and tau P301L human transgenes provided the model...

Gambierol is a marine polyether ladder toxin derived from the dinoflagellate Gambierdiscus toxicus. To date, gambierol has been reported to act either as a partial agonist or as an antagonist of sodium channels or as a blocker of voltage-dependent potassium channels. In this work, we examined the cellular effect of gambierol on cytosolic calcium co...

Azaspiracids (AZAs) are a group of marine toxins recently described that currently includes 20 members. Not much is known about their mechanism of action, although the predominant analog in nature, AZA-1 targets several organs in vivo, including the central nervous system, and exhibits high neurotoxicity in vitro. AZA distribution is increasing glo...

Algal toxins are important from an analytical point of view because they need to be constantly scrutinized owing to the danger they pose to consumers when they concentrate in filter-feeding shellfish or in drinking water and fish. Their chemical diversity is very large, with each group having many analogs. Each group has different pharmacological a...

Advances in transgenic technology as well as in the genetics of Alzheimer disease (AD) have allowed the establishment of animal models that reproduce amyloid-beta plaques and neurofibrillary tangles, the main pathological hallmarks of AD. Among these models, 3xTg-AD mice harboring PS1 M146V , APP Swe and tau P301L human transgenes provided the mode...

Marine toxins accumulate in filter-feeding bivalves. Their presence is a risk to consumers and requires costly control systems to avoid food-safety problems. The mouse bioassay is the method currently used in most countries, but it is being challenged with regards to ethical issues and specificity.There are two options. One uses an analytical metho...