Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used ... more Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, and SK-MEL-28) using the MTT and LDH assays. The ability of compounds to stimulate the production of hydrogen peroxide (H2O2) and to induce mitochondrial dysfunction, the externalization of phosphatidylserine, Caspase-9 activity, and changes in nuclear morphology was also studied on MCF-7 cells. The ability to induce DNA damage was also studied on L929 fibroblasts. The proteasome inhibitory activity was estimated through molecular docking studies. The compounds exhibited IC50 values between 15.35 and 53.34 µM. 12R-hydroxy-bromosphaerol and 12S-hydroxy-bromosphaerol incre...
The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Maize and grass silages are important dietary components for ruminant livestock that influence th... more Maize and grass silages are important dietary components for ruminant livestock that influence the quality of animal products for human consumption, such as milk, in many parts of the world. Infection of plants by fungi able to produce mycotoxins, either in the field or post-harvest, can result in a decrease of silage nutritional quality and, consequently, in milk quality. In this study, 45 maize and grass silage samples were collected from 25 dairy farms located in the north of Portugal. The occurrence of fungi was evaluated in samples, the most frequently isolated species being Aspergillus fumigatus, Dipodascus geotrichum, Mucor circinelloides, Penicillium paneum, and Aspergillus flavus. The mycotoxigenic profile of the fungal species was studied using the ultra-high-performance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UHPLC-MS-IT-TOF) detection. In addition, a new method based on a QuEChERS extraction followed by the UHPLC- tandem mass spectrometry (UHPLC-MS/MS) detection was developed for simultaneous analysis of 39 mycotoxins in silage. A high co-occurrence of Fusarium mycotoxins was found, although at low levels of contamination. Deoxynivalenol and beauvericin were found in more than 82% of maize silage samples. It can be highlighted the low occurrence of Penicillium and Aspergillus toxins in the maize and grass silages studied despite the frequent detection of species of both genera.
In the last decades, due to monitoring programs and strict legislation poisoning incidents occurr... more In the last decades, due to monitoring programs and strict legislation poisoning incidents occurrence provoked by ingestion of naturally contaminated marine organisms has decreased. However, climate change and anthropogenic interference contributed to the expansion and establishment of toxic alien species to more temperate ecosystems. In this work, the coasts of Madeira, São Miguel islands and the northwestern Moroccan coast were surveyed for four groups of lipophilic toxins (yessotoxins, azaspiracids, pectenotoxins, and spirolides), searching for new vectors and geographical tendencies. Twenty-four species benthic organisms were screened using UHPLC-MS/MS technique. We report 19 new vectors for these toxins, six of them with commercial interest (P. aspera, P. ordinaria, C. lampas, P. pollicipes, H. tuberculata and P. lividus). Regarding toxin uptake a south-north gradient was detected. This study contributes to the update of monitoring routines and legislation policies, comprising a wider range of vectors, to better serve consumers and ecosystems preservation.
Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decad... more Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decade its presence has been more pronounced in the temperate waters of the Atlantic. In its last scientific opinion, the European Food Safety Authority (EFSA) stressed the need for data regarding TTX prevalence in European waters. To address EFSA’s concerns, benthic organisms such as mollusks, crustaceans, echinoderms and fish with different feeding habits were collected along the Portuguese continental coast, islands (São Miguel, Azores, and Madeira) and the northwestern Moroccan coast. A total of 165 samples were analyzed by ultra high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) and ultra high performance chromatography mass spectrometry (UHPLC-MS/MS). Geographical tendencies were detected as follows, by descending order: S. Miguel Island (Azores), Moroccan coast, Madeira Island and Portuguese continental coast. The toxin amounts detected were significa...
Acknowledgments: The research leading to these results has received funding from the following FE... more Acknowledgments: The research leading to these results has received funding from the following FEDER cofounded grants: from CDTI (Centre for Technological and Industrial Development), Spain, IDI-20130304 APTAFOOD under ISIP Program, and ITC-20161072 under FEDER-Innterconecta Program. The authors thank Isabel Rivas Morán for her skillful technical assistance and Cristina Carrera (Agrovitis) for helpful advice on the management of vineyards and phenology dates. Jesús María González Jartín was supported by a fellowship from Programa de Formación de Profesorado Universitario (FPU14/00166), Ministerio de Educación, Spain.
A method based on the combined use of ultra performance liquid chromatography coupled to mass spe... more A method based on the combined use of ultra performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight (UPLC-MS-IT-TOF) detection was employed to identify the metabolite production of Aspergillus ochraceus, which is the major cause of food and feed contamination due to ochratoxin A (OTA). Under the proposed chromatographic conditions, the separation and identification of seven metabolites belonging to the family of circumdatins was achieved. Their initial identification was performed through the exact molecular formula, as a function of their accurate mass. Collision induced dissociation (CID) was applied to predict precursor and product ions and elemental composition of each compound was obtained. The elimination of nitrogenous groups followed by successive losses of carbonyl groups is the common fragmentation pathway of circumdatins. With the fragmentation data obtained, an UPLC-MS/MS method was created and optimized to detect circumdatins in corn samples.
In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum ... more In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liq...
Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish P... more Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp.,...
Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ci... more Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs). These phycotoxins are produced mainly by
During official shellfish control for the presence of marine biotoxins in Greece in year 2012, a ... more During official shellfish control for the presence of marine biotoxins in Greece in year 2012, a series of unexplained positive mouse bioassays (MBA) for lipophilic toxins with nervous symptomatology prior to mice death was observed in mussels from Vistonikos Bay-Lagos, Rodopi. This atypical toxicity coincided with (a) absence or low levels of regulated and some non-regulated toxins in mussels and (b) the simultaneous presence of the potentially toxic microalgal species Prorocentrum minimum at levels up to 1.89 × 10 3 cells/L in the area's seawater. Further analyses by different MBA protocols indicated that the unknown toxin was hydrophilic, whereas UPLC-MS/MS analyses revealed the presence of tetrodotoxins (TTXs) at levels up to 222.9 μg/kg. Reviewing of official control data from previous years (2006-2012) identified a number of sample cases with atypical positive to asymptomatic negative MBAs for lipophilic toxins in different Greek production areas, coinciding with periods of P. minimum blooms. UPLC-MS/MS analysis of retained sub-samples from these cases revealed that TTXs were already present in Greek shellfish since 2006, in concentrations ranging between 61.0 and 194.7 μg/kg. To our knowledge, this is the
The separation of PSP toxins using liquid chromatography with a post-column oxidation fluorescenc... more The separation of PSP toxins using liquid chromatography with a post-column oxidation fluorescence detection method was performed with different matrices. The separation of PSP toxins depends on several factors, and it is crucial to take into account the presence of interfering matrix peaks to produce a good separation. The matrix peaks are not always the same, which is a significant issue when it comes to producing good, reliable results regarding resolution and toxicity information. Different real shellfish matrices (mussel, scallop, clam and oyster) were studied, and it was seen that the interference is not the same for each individual matrix. It also depends on the species, sampling location and the date of collection. It was proposed that separation should be accomplished taking into account the type of matrix, as well as the concentration of heptane sulfonate in both solvents, since the mobile phase varies regarding the matrix. Scallop and oyster matrices needed a decrease in ...
Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells a... more Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells are pretreated with thapsigargin before the addition of external calcium. Okadaic acid does not modify the response of mast cells to thapsigargin, while sodium fluoride or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) increases several fold the sensitivity of cells to thapsigargin. On the other hand, pertussis and cholera toxins inhibit the response to thapsigargin. Thapsigargin increases the activity of the Na(+)-H+ exchanger, this effect being blocked by fluoride and not modified by TPA. The metals cadmium and lanthanum completely block the effect of TPA or thapsigargin on the Na(+)-H+ exchanger. The influx of 45Ca in rat mast cells is not modified by thapsigargin, but if cells are treated with thapsigargin before the addition of calcium, the influx is markedly increased in the first 2 min before returning to normal. Our results indicate that exocytosis is modulated by crosstalks between intracellular calcium, cytosolic pH and external calcium.
In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produ... more In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals.
Abstract Azaspiracids and yessotoxins (YTX) are marine toxins that still pose a scientific proble... more Abstract 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 apoptosis. YTX are less well understood, the primary unclear aspect being whether or not they are in fact toxins, since there are no reports of a human intoxication. Possible targets of YTX have been proposed to be adhesion proteins, phosphodiesterases, PKC, the AKAP complex, or calcium pools. It is unclear if this toxin causes apoptosis, autophagia, or both, depending on the cell type. Also, the mechanism of action has been proposed as a basis for several possible therapeutic uses, as anticancer or anti-Alzheimer’s drug.
Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used ... more Seaweeds are a great source of compounds with cytotoxic properties with the potential to be used as anticancer agents. This study evaluated the cytotoxic and proteasome inhibitory activities of 12R-hydroxy-bromosphaerol, 12S-hydroxy-bromosphaerol, and bromosphaerol isolated from Sphaerococcus coronopifolius. The cytotoxicity was evaluated on malignant cell lines (A549, CACO-2, HCT-15, MCF-7, NCI-H226, PC-3, SH-SY5Y, and SK-MEL-28) using the MTT and LDH assays. The ability of compounds to stimulate the production of hydrogen peroxide (H2O2) and to induce mitochondrial dysfunction, the externalization of phosphatidylserine, Caspase-9 activity, and changes in nuclear morphology was also studied on MCF-7 cells. The ability to induce DNA damage was also studied on L929 fibroblasts. The proteasome inhibitory activity was estimated through molecular docking studies. The compounds exhibited IC50 values between 15.35 and 53.34 µM. 12R-hydroxy-bromosphaerol and 12S-hydroxy-bromosphaerol incre...
The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
The 7th Iberian Congress on Cyanotoxins/3rd Iberoamerican Congress on Cyanotoxins
This article is an open access article distributed under the terms and conditions of the Creative... more This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY
Maize and grass silages are important dietary components for ruminant livestock that influence th... more Maize and grass silages are important dietary components for ruminant livestock that influence the quality of animal products for human consumption, such as milk, in many parts of the world. Infection of plants by fungi able to produce mycotoxins, either in the field or post-harvest, can result in a decrease of silage nutritional quality and, consequently, in milk quality. In this study, 45 maize and grass silage samples were collected from 25 dairy farms located in the north of Portugal. The occurrence of fungi was evaluated in samples, the most frequently isolated species being Aspergillus fumigatus, Dipodascus geotrichum, Mucor circinelloides, Penicillium paneum, and Aspergillus flavus. The mycotoxigenic profile of the fungal species was studied using the ultra-high-performance liquid chromatography coupled to mass spectrometry-ion trap-time-of-flight (UHPLC-MS-IT-TOF) detection. In addition, a new method based on a QuEChERS extraction followed by the UHPLC- tandem mass spectrometry (UHPLC-MS/MS) detection was developed for simultaneous analysis of 39 mycotoxins in silage. A high co-occurrence of Fusarium mycotoxins was found, although at low levels of contamination. Deoxynivalenol and beauvericin were found in more than 82% of maize silage samples. It can be highlighted the low occurrence of Penicillium and Aspergillus toxins in the maize and grass silages studied despite the frequent detection of species of both genera.
In the last decades, due to monitoring programs and strict legislation poisoning incidents occurr... more In the last decades, due to monitoring programs and strict legislation poisoning incidents occurrence provoked by ingestion of naturally contaminated marine organisms has decreased. However, climate change and anthropogenic interference contributed to the expansion and establishment of toxic alien species to more temperate ecosystems. In this work, the coasts of Madeira, São Miguel islands and the northwestern Moroccan coast were surveyed for four groups of lipophilic toxins (yessotoxins, azaspiracids, pectenotoxins, and spirolides), searching for new vectors and geographical tendencies. Twenty-four species benthic organisms were screened using UHPLC-MS/MS technique. We report 19 new vectors for these toxins, six of them with commercial interest (P. aspera, P. ordinaria, C. lampas, P. pollicipes, H. tuberculata and P. lividus). Regarding toxin uptake a south-north gradient was detected. This study contributes to the update of monitoring routines and legislation policies, comprising a wider range of vectors, to better serve consumers and ecosystems preservation.
Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decad... more Tetrodotoxin (TTX) is a potent alkaloid typically from tropical ecosystems, but in the last decade its presence has been more pronounced in the temperate waters of the Atlantic. In its last scientific opinion, the European Food Safety Authority (EFSA) stressed the need for data regarding TTX prevalence in European waters. To address EFSA’s concerns, benthic organisms such as mollusks, crustaceans, echinoderms and fish with different feeding habits were collected along the Portuguese continental coast, islands (São Miguel, Azores, and Madeira) and the northwestern Moroccan coast. A total of 165 samples were analyzed by ultra high performance liquid chromatography high resolution mass spectrometry (UHPLC-HRMS) and ultra high performance chromatography mass spectrometry (UHPLC-MS/MS). Geographical tendencies were detected as follows, by descending order: S. Miguel Island (Azores), Moroccan coast, Madeira Island and Portuguese continental coast. The toxin amounts detected were significa...
Acknowledgments: The research leading to these results has received funding from the following FE... more Acknowledgments: The research leading to these results has received funding from the following FEDER cofounded grants: from CDTI (Centre for Technological and Industrial Development), Spain, IDI-20130304 APTAFOOD under ISIP Program, and ITC-20161072 under FEDER-Innterconecta Program. The authors thank Isabel Rivas Morán for her skillful technical assistance and Cristina Carrera (Agrovitis) for helpful advice on the management of vineyards and phenology dates. Jesús María González Jartín was supported by a fellowship from Programa de Formación de Profesorado Universitario (FPU14/00166), Ministerio de Educación, Spain.
A method based on the combined use of ultra performance liquid chromatography coupled to mass spe... more A method based on the combined use of ultra performance liquid chromatography coupled to mass spectrometry-ion trap-time of flight (UPLC-MS-IT-TOF) detection was employed to identify the metabolite production of Aspergillus ochraceus, which is the major cause of food and feed contamination due to ochratoxin A (OTA). Under the proposed chromatographic conditions, the separation and identification of seven metabolites belonging to the family of circumdatins was achieved. Their initial identification was performed through the exact molecular formula, as a function of their accurate mass. Collision induced dissociation (CID) was applied to predict precursor and product ions and elemental composition of each compound was obtained. The elimination of nitrogenous groups followed by successive losses of carbonyl groups is the common fragmentation pathway of circumdatins. With the fragmentation data obtained, an UPLC-MS/MS method was created and optimized to detect circumdatins in corn samples.
In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum ... more In 2012, Tetrodotoxin (TTX) was identified in mussels and linked to the presence of Prorocentrum minimum (P. minimum) in Greece. The connexion between TTX and P. minimum was further studied in this paper. First, the presence of TTX-producer bacteria, Vibrio and Pseudomonas spp, was confirmed in Greek mussels. In addition these samples showed high activity as inhibitors of sodium currents (INa). P. minimum was before associated with neurotoxic symptoms, however, the nature and structure of toxins produced by this dinoflagellate remains unknown. Three P. minimum strains, ccmp1529, ccmp2811 and ccmp2956, growing in different conditions of temperature, salinity and light were used to study the production of toxic compounds. Electrophysiological assays showed no effect of ccmp2811 strain on INa, while ccmp1529 and ccmp2956 strains were able to significantly reduce INa in the same way as TTX. In these samples two new compounds, m/z 265 and m/z 308, were identified and characterized by liq...
Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish P... more Okadaic acid and its analogues are potent phosphatase inhibitors that cause Diarrheic Shellfish Poisoning (DSP) through the ingestion of contaminated shellfish by humans. This group of toxins is transmitted worldwide but the number of poisoning incidents has declined over the last 20 years due to legislation and monitoring programs that were implemented for bivalves. In the summer of 2012 and 2013, we collected a total of 101 samples of 22 different species that were made up of benthic and subtidal organisms such echinoderms, crustaceans, bivalves and gastropods from Madeira, São Miguel Island (Azores archipelago) and the northwestern coast of Morocco. The samples were analyzed by UPLC-MS/MS. Our main objective was to detect new vectors for these biotoxins. We can report nine new vectors for these toxins in the North Atlantic: Astropecten aranciacus, Arbacia lixula, Echinaster sepositus, Holothuria sanctori, Ophidiaster ophidianus, Onchidella celtica, Aplysia depilans, Patella spp.,...
Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ci... more Ciguatera fish poisoning (CFP) is a syndrome caused by the ingestion of fish contaminated with Ciguatoxins (CTXs). These phycotoxins are produced mainly by
During official shellfish control for the presence of marine biotoxins in Greece in year 2012, a ... more During official shellfish control for the presence of marine biotoxins in Greece in year 2012, a series of unexplained positive mouse bioassays (MBA) for lipophilic toxins with nervous symptomatology prior to mice death was observed in mussels from Vistonikos Bay-Lagos, Rodopi. This atypical toxicity coincided with (a) absence or low levels of regulated and some non-regulated toxins in mussels and (b) the simultaneous presence of the potentially toxic microalgal species Prorocentrum minimum at levels up to 1.89 × 10 3 cells/L in the area's seawater. Further analyses by different MBA protocols indicated that the unknown toxin was hydrophilic, whereas UPLC-MS/MS analyses revealed the presence of tetrodotoxins (TTXs) at levels up to 222.9 μg/kg. Reviewing of official control data from previous years (2006-2012) identified a number of sample cases with atypical positive to asymptomatic negative MBAs for lipophilic toxins in different Greek production areas, coinciding with periods of P. minimum blooms. UPLC-MS/MS analysis of retained sub-samples from these cases revealed that TTXs were already present in Greek shellfish since 2006, in concentrations ranging between 61.0 and 194.7 μg/kg. To our knowledge, this is the
The separation of PSP toxins using liquid chromatography with a post-column oxidation fluorescenc... more The separation of PSP toxins using liquid chromatography with a post-column oxidation fluorescence detection method was performed with different matrices. The separation of PSP toxins depends on several factors, and it is crucial to take into account the presence of interfering matrix peaks to produce a good separation. The matrix peaks are not always the same, which is a significant issue when it comes to producing good, reliable results regarding resolution and toxicity information. Different real shellfish matrices (mussel, scallop, clam and oyster) were studied, and it was seen that the interference is not the same for each individual matrix. It also depends on the species, sampling location and the date of collection. It was proposed that separation should be accomplished taking into account the type of matrix, as well as the concentration of heptane sulfonate in both solvents, since the mobile phase varies regarding the matrix. Scallop and oyster matrices needed a decrease in ...
Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells a... more Thapsigargin elicits histamine release on rat mast cells, and this effect is increased if cells are pretreated with thapsigargin before the addition of external calcium. Okadaic acid does not modify the response of mast cells to thapsigargin, while sodium fluoride or the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) increases several fold the sensitivity of cells to thapsigargin. On the other hand, pertussis and cholera toxins inhibit the response to thapsigargin. Thapsigargin increases the activity of the Na(+)-H+ exchanger, this effect being blocked by fluoride and not modified by TPA. The metals cadmium and lanthanum completely block the effect of TPA or thapsigargin on the Na(+)-H+ exchanger. The influx of 45Ca in rat mast cells is not modified by thapsigargin, but if cells are treated with thapsigargin before the addition of calcium, the influx is markedly increased in the first 2 min before returning to normal. Our results indicate that exocytosis is modulated by crosstalks between intracellular calcium, cytosolic pH and external calcium.
In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produ... more In vivo, after administration by gavage to mice and rats, okadaic acid has been reported to produce lesions in liver, small intestine and forestomach. Because several reports differ in the damage detected in different organs, and on okadaic acid distribution after consumption, we determined the toxicity of this compound after oral administration to mice. After 24 hours, histopathological examination showed necrotic foci and lipid vacuoles in the livers of intoxicated animals. By immunohistochemical analysis, we detected this toxin in the liver and kidneys of intoxicated animals. Okadaic acid induces oxidative stress and can be activated in vitro into reactive compounds by the post-mitochondrial S9 fraction, so we studied the okadaic effect on the gene expression of antioxidant and phase II detoxifying enzymes in liver. We observed a downregulation in the expression of these enzymes and a reduction of protein expression of catalase and superoxide dismutase 1 in intoxicated animals.
Abstract Azaspiracids and yessotoxins (YTX) are marine toxins that still pose a scientific proble... more Abstract 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 apoptosis. YTX are less well understood, the primary unclear aspect being whether or not they are in fact toxins, since there are no reports of a human intoxication. Possible targets of YTX have been proposed to be adhesion proteins, phosphodiesterases, PKC, the AKAP complex, or calcium pools. It is unclear if this toxin causes apoptosis, autophagia, or both, depending on the cell type. Also, the mechanism of action has been proposed as a basis for several possible therapeutic uses, as anticancer or anti-Alzheimer’s drug.
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