يعرض 1 - 10 نتائج من 82 نتيجة بحث عن '"Luis M. Botana"', وقت الاستعلام: 1.60s تنقيح النتائج
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    دورية أكاديمية

    المصدر: Toxins, Vol 8, Iss 7, p 208 (2016)

    الوصف: Current regulation for marine toxins requires a monitoring method based on mass spectrometric analysis. This method is pre-targeted, hence after searching for pre-assigned masses, it identifies those compounds that were pre-defined with available calibrants. Therefore, the scope for detecting novel toxins which are not included in the monitoring protocol are very limited. In addition to this, there is a poor comprehension of the toxicity of some marine toxin groups. Also, the validity of the current approach is questioned by the lack of sufficient calibrants, and by the insufficient coverage by current legislation of the toxins reported to be present in shellfish. As an example, tetrodotoxin, palytoxin analogs, or cyclic imines are mentioned as indicators of gaps in the system that require a solid comprehension to assure consumers are protected.

    وصف الملف: electronic resource

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    المصدر: Chemical Research in Toxicology. 34:865-879

    الوصف: 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 pharmacological approaches were employed to evaluate the role of anion channels on the AZA effects that demonstrated that cellular anion dysregulation was involved in the toxic effects of these compounds. The results presented here demonstrated that volume regulated anion channels (VRACs) are affected by this group of toxins, and, because there is not any specific activator of VRACs besides the intracellular application of GTPγ-S molecule, this group of natural compounds could represent a powerful tool to analyze the role of these channels in cellular homeostasis. In addition to this, in this work, a detailed pharmacological approach was performed in order to elucidate the anion channels present in human HEK293 cells as well as their regulation by the marine toxins azaspiracids. Altogether, the data presented here demonstrated that the effect of azaspiracids in human cells was completely dependent on ATP-regulated anion channels, whose upregulation by these toxins could lead to regulatory volume decrease and underlie the reported toxicity of these compounds.

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    المصدر: Talanta. 189:622-628

    الوصف: A UPLC-MS/MS method has been developed for identification and quantification of hydrophilic and lipophilic marine toxins. The method included the determination of 14 toxins of STX group, 15 lipophilic toxins, 15 toxins of the TTX group and DA. LODs and LOQs for STX group were significantly improved in comparison to the official validated methods and at the same level than other UPLC-MS/MS published methods. The same for lipophilic toxins, with better LODs and LOQs than the EU official method. LOD and LOQ for DA were higher than those obtained with the EU official method. While for TTXs LOD and LOQ were comparable to other validated methods. Validation studies demonstrated acceptable method performance characteristics for linearity, and repeatability between-batch and within-batch. The study demonstrated that the UPLC-MS/MS method provides an excellent tool to determinate hydrophilic and lipophilic toxins and therefore it could be appropriate for routine testing and interlaboratory validation.

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    المصدر: Proceedings of 1st International Electronic Conference on Toxins.

    الوصف: Palytoxin (PLTX) is a marine toxin that nowadays is recognized amongst the most toxic compounds isolated from natural products. Originally, the toxin was only identified in a single tidal pool of the island of Maui (Hawaii). Currently, this compound is considered as an emergent toxin in Europe and its prevalence in continental European waters has increased during the last years. The high toxicity of palytoxin is related with the binding to the Na+-K+ ATPase, converting this ubiquitously distributed enzyme in a permeant cation channel [1-3]. Several reports have shown that this toxin is responsible for human fatal intoxications, either after inhalation of toxin-containing marine aerosols or after ingestion of marine products contaminated with PLTX, such as crabs, groupers, mackerel, and parrotfish. So far, different groups have explored the acute oral toxicity of PLTX in mice however, discrepancies in the PLTX source as well as in the monitoring time for the toxic effects yielded controversial results. Although the presence of palytoxin in marine products is not yet currently regulated in Europe, the European Food Safety Authority (EFSA) expressed its opinion on PLTX toxicity and prompted the need to obtain more data regarding the in vivo toxicity of this compound [4]. Therefore, in this study, the acute and chronic toxicity of palytoxin was evaluated after oral administration of the toxin to mice either in a single dose and in a follow-up period of 96 hours or after chronic administration during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX, much lower than that observed in the acute experiments, and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. Therefore, these data indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods remarking the need to further evaluate the potential teratogenic effects of this emerging marine toxin in mammals. References Artigas, P.; Gadsby, D.C. Ion occlusion/deocclusion partial reactions in individual palytoxin-modified Na+/K+ pumps. Ann N Y Acad Sci 2003, 986, 116-126. Artigas, P.; Gadsby, D.C. Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels. Proc Natl Acad Sci U S A 2003, 100, 501-505. Artigas, P.; Gadsby, D.C. Large diameter of palytoxin-induced Na+/K+ pump channels and modulation of palytoxin interaction by Na+/K+ pump ligands. J Gen Physiol 2004, 123, 357-376. EFSA. Panel on contaminants in the food chain (CONTAM). Scientific Opinion on marine biotoxins in shellfish–Palytoxin group. EFSA Journal, 2009; Vol. 7, p 1393.

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    المصدر: Proceedings of 1st International Electronic Conference on Toxins.

    الوصف: Tetrodotoxin (TTX) is a very toxic compound responsible for human intoxications after ingestion of contaminated fishery products. Although TTX was initially associated mainly with human fatalities occurring in Asiatic countries[1], nowadays has expanded to other regions including European countries. In Europe, the first non-fatal human intoxications by TTX was reported more than 10 years ago after the ingestion of a Charonia lampas trumpet shell captured in the Portuguese coast and commercialized in Spain[2]. Since then, during the last decade, the presence of the TTX-containing pufferfish Lagocephalus sceleratus has been reported in European coasts, mainly in the Mediterranean Sea[3,4] with some fish tissues containing TTXs amounts as high as 2 mg/kg[5]. Moreover, an increasing concern regarding food safety has been raised after the detection of TTX in mussels, oysters and clams harvested in UK, Greece, the Netherlands[6-8] and Spain. The current European legislation in marine toxins did not yet regulated the levels of TTX in fishery products, and nowadays the presence of the toxin is only regularly monitored in the Netherlands although the European Food Safety Authority (EFSA) has recommended the level of 44 µg/kg TTXs for routine monitoring since, at this dose, no adverse effects were observed in humans. Considering initial data on the acute oral toxicity of TTX and in view of the EFSA opinion remarking the need for additional chronic toxicity studies to further reduce the uncertainty of the likely future toxin regulation. In this work, the oral chronic toxicity of TTX using doses of 25, 44, 75 and 125 µg/kg and an observation period of 28 days was explored in female mice using protocols internationally validated to test the toxicity of chemicals. The data presented here indicated that 25 and 44 µg/kg of TTX did not cause neither blood biochemical nor behavioral alterations in mice, while at the dose of 125 µg/kg kidney and heart alterations were observed under electron microscopy analysis. Therefore, the data presented here indicate that the safety TTX dose proposed by EFSA is low enough to prevent human adverse effects, while caution should be taken in the presence of higher TTX doses. References: Bane, V.; Lehane, M.; Dikshit, M.; O'Riordan, A.; Furey, A. Tetrodotoxin: chemistry, toxicity, source, distribution and detection. Toxins 2014, 6, 693-755. Rodriguez, P.; Alfonso, A.; Vale, C.; Alfonso, C.; Vale, P.; Tellez, A.; Botana, L.M. First Toxicity Report of Tetrodotoxin and 5,6,11-TrideoxyTTX in the Trumpet Shell Charonia lampas lampas in Europe. Analytical Chemistry 2008, 80. Rambla-Alegre, M.; Reverte, L.; Del Rio, V.; de la Iglesia, P.; Palacios, O.; Flores, C.; Caixach, J.; Campbell, K.; Elliott, C.T.; Izquierdo-Munoz, A., et al. Evaluation of tetrodotoxins in puffer fish caught along the Mediterranean coast of Spain. Toxin profile of Lagocephalus sceleratus. Environ Res 2017, 158, 1-6. Katikou, P.; Georgantelis, D.; Sinouris, N.; Petsi, A.; Fotaras, T. First report on toxicity assessment of the Lessepsian migrant pufferfish Lagocephalus sceleratus (Gmelin, 1789) from European waters (Aegean Sea, Greece). Toxicon 2009, 54, 50-55. Leonardo, S.; Kiparissis, S.; Rambla-Alegre, M.; Almarza, S.; Roque, A.; Andree, K.B.; Christidis, A.; Flores, C.; Caixach, J.; Campbell, K., et al. Detection of tetrodotoxins in juvenile pufferfish Lagocephalus sceleratus (Gmelin, 1789) from the North Aegean Sea (Greece) by an electrochemical magnetic bead-based immunosensing tool. Food Chem 2019, 290, 255-262. Katikou, P. Public Health Risks Associated with Tetrodotoxin and Its Analogues in European Waters: Recent Advances after The EFSA Scientific Opinion. Toxins 2019, 11. Turner, A.D.; Powell, A.; Schofield, A.; Lees, D.N.; Baker-Austin, C. Detection of the pufferfish toxin tetrodotoxin in European bivalves, England, 2013 to 2014. Eurosurveillance 2015, 20, 21009. Vlamis, A.; Katikou, P.; Rodriguez, I.; Rey, V.; Alfonso, A.; Papazachariou, A.; Zacharaki, T.; Botana, A.M.; Botana, L.M. First Detection of Tetrodotoxin in Greek Shellfish by UPLC-MS/MS Potentially Linked to the Presence of the Dinoflagellate Prorocentrum minimum. Toxins 2015, 7, 1779-1807.

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  7. 7

    المصدر: Proceedings of 1st International Electronic Conference on Toxins.

    الوصف: Food supplements containing mussel extracts are becoming popular in human diet, providing high levels of proteins, omega-3 polyunsatured fatty acid (PUFAs), iodine and carbohydrates [1, 2]. Besides the beneficial effects and bioactives that mussels may yield, it is vital to consider the potential harmful phycotoxins that can be present in mussel extracts and marine dietary supplements. Recently, we have detected for the first time the marine toxin 13-desmethyl spirolide C in food supplements containing green lipped mussels of Perna canaliculus at levels up to 98 µg/kg [3]. In this work, we provide new data about the presence of pinnatoxin-G (trace amounts) in the dietary supplements intended for human consumption after the analysis of the green lipped mussel powder by UPLC-MS/MS. Moreover, the status of microalgae phycotoxin contaminants is also assessed in these products and in animal dietary supplements which contained 13-desmethyl spirolide C at levels up to 39 µg/kg. The mechanism of action of spirolides and pinnatoxins is associated with the blockage of the muscarinic and nicotinic receptors (mAChR and nAChR) on the nervous system. Despite the fact that human intoxications have not been reported, it is important to identify the impact of such toxins on public health since dietary products constitute an important part of the global market. References: [1] C.S. Cobb, E. Ernst, Systematic review of a marine nutriceutical supplemnt in clinical trials for arthritis: The effectiveness of the New Zealand green-lipped mussel Perna canaliculus, Clin. Rheumatol., 25 (2006) 275-284. [2] A. Treschow, L. Hodges, P. Wright, P. Wynne, N. Kalafatis, T. Macrides, Novel Anti-Inflammatory omega-3 PUFAs From the New Zealand Green-Lipped Mussel, Perna Canaliculus, Comp Biochem Physiol B Biochem Mol Biol., 147 (2007) 645-656. [3] P. Otero, C. Vale, A. Boente-Juncal, C. C., M.C. Louzao, L. Botana, Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis Toxins, 12(10) (2020) 613.

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    المصدر: Proceedings of 1st International Electronic Conference on Toxins.

    الوصف: Azaspiracids (AZAs) comprise a group of marine toxins first documented in the Netherlands after ingestion of contaminated mussels, harvested in Ireland coasts, by the end of the last century [1-3]. Azaspiracids are known to be produced by dinoflagellates belonging to the genera Azadinium and Amphidoma [4]. In recent years, part of the research on marine toxins effects on human health have focused on their chronic effects. The presence of azaspiracid in fishery products has been regulated in Europe establishing a limit of 160 μg kg-1 AZA equivalents [5]. Since then, several acute in vitro studies were undertaken to elucidate their mechanism of action, but the results obtained showed great controversy regarding the possible cellular targets of AZAs that could contribute to the symptomatology elicited in humans after ingestion of contaminated fishery products. Our group has recently described that these toxins partially blocked sodium entry into the cells and caused cytoskeletal alterations [6], however the effect of these toxins on ion channels remains almost completely unexplored. Therefore, the main aim of our study was to gain more insight on the effects of azaspiracids on ionic homeostasis and cell volume regulation [7]. Thus, electrophysiological effects of nanomolar concentrations of azaspiracids (50 nM) after a 15-20 h exposition of human embryonic kidney cells (HEK293) which express the human Nav1.7 alpha subunit of the sodium channel were determined. Here, using electrophysiological techniques combined with several pharmacological approaches, we demonstrated that AZA-1 elicited a significant increase in anion efflux that could account for the pathophysiology observed in human intoxications. References McMahon, T. Winter toxicity of unknown aetiology in mussels. Harmful Algae News 1996, 14, 2. Ofuji, K.; Satake, M.; McMahon, T.; Silke, J.; James, K.J.; Naoki, H.; Oshima, Y.; Yasumoto, T. Two analogs of azaspiracid isolated from mussels, Mytilus edulis, involved in human intoxication in Ireland. Nat Toxins 1999, 7, 99-102. Satake, M.; Ofuji, K.; Naoki, H.; James, K.J.; Furey, A.; McMahon, T.; Silke, J.; Yasumoto, T. Azaspiracid, a New Marine Toxin Having Unique Spiro Ring Assemblies, Isolated from Irish Mussels, Mytilus edulis. Journal of the American Chemical Society 1998, 120, 9967-9968. Wietkamp, S.; Krock, B.; Clarke, D.; Vos, D.; Salas, R.; Kilcoyne, J.; Tillmann, U. Distribution and abundance of azaspiracid-producing dinophyte species and their toxins in North Atlantic and North Sea waters in summer 2018. PLOS ONE 2020, 15, e0235015. European Commission. Regulation of the European Parliament and of the Council of 29 April 2004 laying down specific rules for the organisation of official controls on products of animal origin intended for human consumption, 854/2004/EC. In Official Journal, 2004; Vol. 50. Boente-Juncal, A.; Raposo-Garcia, S.; Costas, C.; Louzao, M.C.; Vale, C.; Botana, L.M. Partial Blockade of Human Voltage-Dependent Sodium Channels by the Marine Toxins Azaspiracids. Chemical research in toxicology 2020, 10.1021/acs.chemrestox.0c00216. Vale, C.; Nicolaou, K.C.; Frederick, M.O.; Vieytes, M.R.; Botana, L.M. Cell volume decrease as a link between azaspiracid-induced cytotoxicity and c-Jun-N-terminal kinase activation in cultured neurons. Toxicol Sci 2010, 113, 158-168.

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    المصدر: Chemical research in toxicology. 33(10)

    الوصف: Azaspiracid toxins were first identified at the end of the last century in Irish mussels, and during the last two decades considerable 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, thereby incorporating into the food chain and causing human intoxications. Among the cellular effects of azaspiracids, inhibition of spikes in neurons and hyperpolarization of the neuronal membrane potential have been reported; however, the underlying processes leading to these effects were never elucidated. In this regard, initial studies reported no activity of the toxin in neuronal voltage-gated sodium channels, and a recent work described no effect of azaspiracid-1 on the inactivation kinetics of voltage-gated sodium channels; however, the relationship between the known alterations of the cytoskeleton caused by these toxins and their effects on ion channels has never been evaluated. In this work, the cytotoxic effect of azaspiracids was evaluated in human cells as well as their activity on voltage-gated sodium channels and in cell morphology in order to unravel the cellular targets involved in the mechanism of action of this group of marine toxins. The data reported here demonstrate, for the first time, that both azaspiracid-1 and azaspiracid-2 caused a rapid concentration-dependent inhibition of the amplitude of voltage-gated sodium currents without affecting their inactivation kinetics, an effect that was increased after long-term treatment of the cells with the toxin. Simultaneously, long-term exposure of the cells to azaspiracids caused a profound alteration of the cell cytoskeleton and decreased the metabolic activity of human cells. Altogether, the data presented here indicate that the partial blockade of voltage-gated sodium channels by these toxins is not related with their effect on the actin cytoskeleton. However, since azaspiracids are common toxins in European waters, their effect on voltage-gated sodium channels, first reported here, should be considered to avoid synergistic toxicity with other marine toxins that are known potent blockers of sodium channels such as the saxitoxins and tetrodotoxins, but further studies are needed in order to elucidate how these compounds alter ion homeostasis.

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    المساهمون: Universidade de Santiago de Compostela. Departamento de Farmacoloxía, Farmacia e Tecnoloxía Farmacéutica

    المصدر: Toxins, Vol 12, Iss 613, p 613 (2020)
    Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela
    instname
    Minerva: Repositorio Institucional de la Universidad de Santiago de Compostela
    Universidad de Santiago de Compostela (USC)
    Toxins
    Volume 12
    Issue 10

    الوصف: 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 seafood products from non-European locations, including mussels Mytilus chilensis from Chile, clams Tawerea gayi and Metetrix lyrate from the Southeast Pacific and Vietnam, and food supplements based on mussels formulations of Perna canaliculus from New Zealand. All these products were purchased from European Union markets and they were analyzed by UPLC-MS/MS. Results showed the presence of the emerging pinnatoxin-G in mussels Mytilus chilensis at levels up to 5.2 µ
    g/kg and azaspiracid-2 and pectenotoxin-2 in clams Tawera gayi up to 4.33 µ
    g/kg and 10.88 µ
    g/kg, respectively. This study confirms the presence of pinnatoxins in Chile, one of the major mussel producers worldwide. Chromatograms showed the presence of 13-desmethyl spirolide C in dietary supplements in the range of 33.2&ndash
    97.9 µ
    g/kg after an extraction with water and methanol from 0.39 g of the green lipped mussels powder. As far as we know, this constitutes the first time that an emerging cyclic imine toxin in dietary supplements is reported. Identifying new matrix, locations, and understanding emerging toxin distribution area are important for preventing the risks of spreading and contamination linked to these compounds.

    وصف الملف: application/pdf