RESUMEN
The acute oral toxicity of a new palytoxin congener, 42-hydroxy-palytoxin (42-OH-PLTX), was investigated in female CD-1 mice. The toxin (300-1697 µg/kg), administered by gavage, induced scratching, jumping, respiratory distress, cyanosis, paralysis and death of mice, with an LD50 of 651 µg/kg (95% confidence limits: 384-1018 µg/kg) within 24 h. Hematoclinical analyses showed increased plasma levels of lactate dehydrogenase and aspartate-aminotransferase at doses of 600 µg/kg and above, as well as of alanine-aminotransferase, creatine phosphokinase and potassium ions at ≥ 848 µg/kg. Histology revealed inflammatory lesions in the non-glandular area of the stomach of mice that survived up to 24 h after gavage (424-1200 µg/kg). Although no histological alterations were seen in skeletal and cardiac muscles, changes in some plasma biomarkers (creatine phosphokinase, lactate dehydrogenase) suggested involvement of these tissues in 42-OH-PLTX oral toxicity, in agreement with epidemiological data on seafood poisonings ascribed to palytoxins. Complete recovery of the tissue and hematological changes was observed two weeks post-exposure. Furthermore, 42-OH-PLTX induced in vitro delayed erythrocyte hemolysis at concentrations similar to those of PLTX (EC50 = 7.6 and 13.2 x 10⻹² M, respectively). This hemolysis could be completely neutralized by a monoclonal anti-PLTX antibody. The in vivo data, together with the in vitro data recorded for 42-OH-PLTX, seem to indicate Na+/K+-ATPase as one of the key cellular targets of this toxin.
Asunto(s)
Venenos de Cnidarios/toxicidad , Piranos/toxicidad , Estómago/patología , Administración Oral , Animales , Anticuerpos Monoclonales , Biomarcadores/sangre , Cromatografía Liquida , Venenos de Cnidarios/administración & dosificación , Femenino , Hemólisis/efectos de los fármacos , Técnicas Histológicas , Dosificación Letal Mediana , Espectrometría de Masas , Ratones , Piranos/administración & dosificaciónRESUMEN
Molluscs of many sorts, which are high in protein and trace minerals, have always been a substantial portion of the human diet. A great variety of mollusc species are therefore of commercial importance throughout the world. Episodes of poisoning occasionally happen to the consumers of molluscs, the main hazard being represented by bivalve molluscs. These organisms are filter-feeders, feeding mainly on a wide range of phytoplankton species. Among the thousands of species of microscopic algae at the base of the marine food chain, there are a few dozen which produce potent toxins. One major category of impact occurs when toxic phytoplankton are filtered from the water as food by shellfish, which then accumulate the algal toxins to levels which can be lethal to humans. Incidences of poisoning related to marine algal toxins come under the main categories of paralytic shellfish poisoning (PSP), neurotoxic shellfish poisoning (NSP), diarrhetic shellfish poisoning (DSP), and amnesic shellfish poisoning (ASP), depending upon the toxins and the symptoms that they cause. Since the beginning of the 1990s, a research program has been initiated to examine the toxin profiles in mussels from the Adriatic Sea. Since then, a number of polyether toxins have been isolated and characterized, some of which represent new additions to the DSP class of biotoxins. During this investigation, new types of toxins have also been isolated. The recent application of LC-MS methods for the detection of Adriatic marine biotoxins made it possible to speed up the analysis of toxic samples.
Asunto(s)
Bivalvos/química , Bivalvos/microbiología , Vectores de Enfermedades , Enfermedades Transmitidas por los Alimentos/patología , Toxinas Marinas/química , Toxinas Marinas/toxicidad , Fitoplancton/química , Alimentos Marinos , Animales , HumanosRESUMEN
We have studied the death response induced by yessotoxin (YTX) in cultured HeLa cells, and have compared it to that triggered by okadaic acid (OA) in the same experimental system. Sub-nanomolar concentrations of YTX were found to induce HeLa cell death after a 48-96-h incubation. YTX caused loss of intact poly(ADP-ribose)-polymerase (PARP) in HeLa cells, and detection of the 85kDa fragment, which is indicative of proteolytic attack by caspases. Measurements of caspase activities using extracts prepared from YTX-treated cells and substrates of the caspase-3/7 and caspase-2 isoforms, showed that the relative proteolysis of caspase-3/7 substrate was about eight-fold higher than that of caspase-2, the levels of which were about twice those measured with extracts from control cells. These findings were matched by Western blot analyses of caspase-2, -3 and -7 in HeLa cell extracts, which showed that the levels of pro-caspase-2 were not greatly affected by YTX treatment, whereas pro-caspase-3 and -7 were activated in YTX-treated cells. Taken together, these data complement others previously obtained with OA, and support the notion that caspase isoforms involved in cell death induced by OA and YTX are cell- and toxin-specific.
Asunto(s)
Caspasas/farmacología , Muerte Celular , Inhibidores Enzimáticos/efectos adversos , Éteres Cíclicos/efectos adversos , Venenos de Moluscos/efectos adversos , Ácido Ocadaico/efectos adversos , Oxocinas/efectos adversos , Western Blotting , Relación Dosis-Respuesta a Droga , Células HeLa , Humanos , IsomerismoRESUMEN
A detailed analysis of the toxic composition in the hepatopancreas of mussels from northern Adriatic sea has been performed. Along with some polyether toxins of DSP (diarrhetic shellfish poisoning) type, such as yessotoxin and its analogues, which are responsible for a variety of human seafood poisonings throughout the world, we have now isolated a new type of toxin, the chlorosulfolipid 1, which is completely different in structure from the polyether DSP-toxins isolated so far. The structural determination of the new toxin, including its absolute stereochemistry, has been performed by extensive NMR analysis and molecular mechanics and dynamics calculations.
Asunto(s)
Bivalvos/química , Sistema Digestivo/química , Lípidos/química , Lípidos/toxicidad , Toxinas Marinas/química , Animales , Línea Celular , Supervivencia Celular/efectos de los fármacos , Enfermedades Transmitidas por los Alimentos/etiología , Humanos , Lípidos/aislamiento & purificación , Toxinas Marinas/aislamiento & purificación , Agua de Mar , MariscosRESUMEN
The diarrhetic shellfish toxin composition in the digestive glands of mussels from the northern Adriatic sea was investigated. Along with known yessotoxins, identified by comparison of their chromatographic and spectral properties with those reported in the literature, we isolated a new analogue of yessotoxin, 42,43,44,45,46,47,55-heptanor-41-oxohomoyessotoxin, 1. Its structure was determined by (1)H NMR spectroscopy and mass spectrometry.
Asunto(s)
Bivalvos/química , Sistema Digestivo/química , Éteres Cíclicos/aislamiento & purificación , Oxocinas , Animales , Sistema Digestivo/anatomía & histología , Éteres Cíclicos/química , Europa (Continente) , Espectroscopía de Resonancia Magnética/métodos , Espectrometría de Masas/métodos , Venenos de MoluscosRESUMEN
The contamination of shellfish with marine biotoxins derived from microalgae represents a serious problem for shellfish industries and public health. This study investigated the composition of diarrhetic shellfish toxins in the digestive glands of mussels from the Northern Adriatic Sea. Along with known yessotoxins, identified by comparison of their chromatographic and spectral properties with those reported in the literature, we isolated a new analogue of yessotoxin, carboxyhomoyessotoxin, whose structure was determined by mass spectrometry and (1)H NMR spectroscopy.
Asunto(s)
Bivalvos/química , Éteres Cíclicos/química , Venenos de Moluscos/química , Oxocinas , Animales , Cromatografía Líquida de Alta Presión , Éteres Cíclicos/aislamiento & purificación , Glándulas Exocrinas/química , Italia , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura Molecular , Venenos de Moluscos/aislamiento & purificaciónRESUMEN
A clonal culture of Alexandrium andersoni, obtained from germination of a resting cyst, collected from the Gulf of Naples, was found positive for PSP toxicity by mouse bioassay. The toxicity profile of this dinoflagellate consists mainly of toxins belonging to the saxitoxin class, in particular of Saxitoxin (STX) and Neosaxitoxin (NEO), as determined by a wide MS and (1)H NMR analysis. This represents the first report of the presence of A. andersoni in the Mediterranean Sea, as well as of its toxicity.
Asunto(s)
Dinoflagelados , Saxitoxina/análogos & derivados , Saxitoxina/toxicidad , Animales , Cromatografía en Capa Delgada , Dinoflagelados/química , Dinoflagelados/clasificación , Italia , Masculino , Mar Mediterráneo , Ratones , Saxitoxina/aislamiento & purificación , Mariscos/toxicidad , Espectrofotometría UltravioletaRESUMEN
A detailed analysis of the secondary metabolites of the Caribbean sponge Verongula gigantea has been performed. A number of bromotyrosine derivatives, 1, 2, and 6-17, were identified, one of which (17) is a novel compound. Its structure was determined on the basis of spectroscopic evidence. Additionally, aureol (18) and 5, 6-dibromo-N,N-dimethyltryptamine (19) were isolated from one of the five analyzed specimens.
Asunto(s)
Poríferos/química , Animales , Cromatografía Líquida de Alta Presión , Poríferos/metabolismo , Espectrometría de Masa Bombardeada por Átomos Veloces , Espectrofotometría Infrarroja , Espectrofotometría UltravioletaRESUMEN
A detailed analysis of the secondary metabolites of the sponge Aplysina cauliformis has been performed. Eight compounds were identified, two of which (13 and 14) are new bromotyrosine derivatives whose structures were determinated from spectroscopic evidence, including 2D NMR. The new compounds were analyzed for cytotoxic activity, and compound 14 was shown to inhibit mammalian protein synthesis and cell proliferation.
RESUMEN
The diarrhetic shellfish toxin composition in the hepatopancreas of mussels from the northern Adriatic sea was investigated. The major toxins were shown to be yessotoxin (YTX), homoyessotoxin (homoYTX) and 45-hydroxyyessotoxin (45-OHYTX), identified by comparison of their chromatographic and spectral properties with those reported in the literature.
Asunto(s)
Bivalvos/química , Sistema Digestivo/química , Éteres Cíclicos/aislamiento & purificación , Toxinas Marinas/aislamiento & purificación , Oxocinas , Fitoplancton/química , Animales , Cromatografía Líquida de Alta Presión , Italia , Toxinas Marinas/química , Toxinas Marinas/clasificación , Venenos de Moluscos , Ácido Ocadaico/química , Ácido Ocadaico/aislamiento & purificaciónRESUMEN
This study investigated the composition of diarrhoetic shellfish toxins in the hepatopancreas of mussels from the northern Adriatic Sea. The major toxins were shown to be yessotoxin, identified by its chromatographic properties and spectral data, and okadaic acid, detected both by fluorometric high-performance liquid chromatography and by comparison of its spectral properties with those of an authentic sample.
Asunto(s)
Bivalvos , Éteres Cíclicos/análisis , Venenos de Moluscos/química , Oxocinas , Animales , Cromatografía Líquida de Alta Presión , Éteres Cíclicos/aislamiento & purificación , Éteres Cíclicos/toxicidad , Masculino , Mar Mediterráneo , Ratones , Venenos de Moluscos/toxicidad , Ácido Ocadaico/análisisRESUMEN
A new polymeric pyridinium alkaloid named amphitoxin [2] has been isolated from Amphimedon compressa, and its structure determined by spectroscopic analysis. In laboratory feeding experiments, crude extracts and purified amphitoxin [2] from A. compressa at lower than natural concentration levels effectively deterred feeding of a generalist predatory Caribbean reef fish, Thalassoma bifasciatum.
Asunto(s)
Conducta Alimentaria/efectos de los fármacos , Toxinas Marinas/farmacología , Poríferos/química , Compuestos de Piridinio/farmacología , Animales , Cromatografía Líquida de Alta Presión , Cromatografía por Intercambio Iónico , Peces/fisiología , Espectroscopía de Resonancia Magnética , Toxinas Marinas/química , Toxinas Marinas/aislamiento & purificación , Estructura Molecular , Peso Molecular , Compuestos de Piridinio/química , Compuestos de Piridinio/aislamiento & purificación , Espectrofotometría UltravioletaRESUMEN
Three novel sterols with a rare D-ring unsaturation were isolated from the marine sponge Topsentia aurantiaca and identified as 5 alpha-cholest-14-ene-3 beta,16 alpha-diol (2), 24R-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (3), and 24S-ethyl-5 alpha-cholest-14-ene-3 beta,16 alpha-diol (4). The sponge also elaborates a further D-ring unsaturated sterol, 5 alpha-cholest-15-en-3 beta-ol (1), which has been previously described only as a synthetic product. All the 1H and 13C nuclear magnetic resonances of compounds 1 and 2 were assigned to the relevant protons and carbons by bidimensional COSY, HETCOR, and HMQC nuclear magnetic resonance experiments.
Asunto(s)
Colestanoles/química , Esteroles/química , Cromatografía Líquida de Alta Presión , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Estructura MolecularRESUMEN
The CHCl3 extract of the Mediterranean sponge Clathrina clathrus was shown to contain three new sterols: (22 E)-3 beta-hydroxycholesta-5,8,22-trien-7-one (1), (22 E, 24 xi)-3 beta-hydroxy-24-methylcholesta-5,8,22-trien-7-one (2), and (22 E, 24 xi)-3 beta-hydroxy-24-ethylcholesta-5,8,22-trien-7-one (3), whose structures were elucidated on the basis of physico-chemical evidence.