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Marine Drugs Mar 2010In this review, we focus on processes, organs and systems targeted by the marine toxins yessotoxin (YTX), okadaic acid (OA) and palytoxin (PTX). The effects of YTX and... (Review)
Review
In this review, we focus on processes, organs and systems targeted by the marine toxins yessotoxin (YTX), okadaic acid (OA) and palytoxin (PTX). The effects of YTX and their basis are analyzed from data collected in the mollusc Mytilus galloprovincialis, the annelid Enchytraeus crypticus, Swiss CD1 mice and invertebrate and vertebrate cell cultures. OA and PTX, two toxins with a better established mode of action, are analyzed with regard to their effects on development. The amphibian Xenopus laevis is used as a model, and the Frog Embryo Teratogenesis Assay-Xenopus (FETAX) as the experimental protocol.
Topics: Acrylamides; Animals; Annelida; Cell Line; Cnidarian Venoms; Embryo, Nonmammalian; Immune System; Mice; Mollusk Venoms; Mytilus; Okadaic Acid; Oxocins; Xenopus laevis
PubMed: 20411120
DOI: 10.3390/md8030658 -
Toxins Jul 2021Two high-mass polar compounds were observed in aqueous side-fractions from the purification of okadaic acid () and dinophysistoxin-2 () from blooms in Spain and Norway....
Identification of 24--β-d-Glycosides and 7-Deoxy-Analogues of Okadaic Acid and Dinophysistoxin-1 and -2 in Extracts from Blooms, and Cultures, and Shellfish in Europe, North America and Australasia.
Two high-mass polar compounds were observed in aqueous side-fractions from the purification of okadaic acid () and dinophysistoxin-2 () from blooms in Spain and Norway. These were isolated and shown to be 24--β-d-glucosides of and ( and , respectively) by nuclear magnetic resonance (NMR) spectroscopy, mass spectrometry, and enzymatic hydrolysis. These, together with standards of , , dinophysistoxin-1 (), and a synthetic specimen of 7-deoxy- (), combined with an understanding of their mass spectrometric fragmentation patterns, were then used to identify -, the 24--β-d-glucoside of dinophysistoxin-1 (), , 7-deoxy- (), and 7-deoxy- () in a range of extracts from blooms, cultures, and contaminated shellfish from Spain, Norway, Ireland, Canada, and New Zealand. A range of cultures was also examined by liquid chromatography-high resolution tandem mass spectrometry (LC-HRMS/MS) and was found to contain , , , and . However, although - were not detected in these cultures, low levels of putative glycosides with the same exact masses as and were present. The potential implications of these findings for the toxicology, metabolism, and biosynthesis of the okadaic acid group of marine biotoxins are briefly discussed.
Topics: Animals; Australasia; Biological Monitoring; Bivalvia; Dinoflagellida; Europe; Food Contamination; Glycosides; North America; Okadaic Acid; Shellfish
PubMed: 34437381
DOI: 10.3390/toxins13080510 -
Use of okadaic acid to identify relevant phosphoepitopes in pathology: a focus on neurodegeneration.Marine Drugs May 2013Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase... (Review)
Review
Protein phosphorylation is involved in the regulation of a wide variety of physiological processes and is the result of a balance between protein kinase and phosphatase activities. Biologically active marine derived compounds have been shown to represent an interesting source of novel compounds that could modify that balance. Among them, the marine toxin and tumor promoter, okadaic acid (OA), has been shown as an inhibitor of two of the main cytosolic, broad-specificity protein phosphatases, PP1 and PP2A, thus providing an excellent cell-permeable probe for examining the role of protein phosphorylation, and PP1 and PP2A in particular, in any physiological or pathological process. In the present work, we review the use of okadaic acid to identify specific phosphoepitopes mainly in proteins relevant for neurodegeneration. We will specifically highlight those cases of highly dynamic phosphorylation-dephosphorylation events and the ability of OA to block the high turnover phosphorylation, thus allowing the detection of modified residues that could be otherwise difficult to identify. Finally, its effect on tau hyperhosphorylation and its relevance in neurodegenerative pathologies such as Alzheimer's disease and related dementia will be discussed.
Topics: Animals; Epitopes; Humans; Neurodegenerative Diseases; Okadaic Acid; Phosphorylation; Protein Phosphatase 1; Protein Phosphatase 2; tau Proteins
PubMed: 23697949
DOI: 10.3390/md11051656 -
Archives of Toxicology Aug 2021The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms...
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 fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3-36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3-36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.
Topics: Animals; Cyproheptadine; Diarrhea; Enzyme Inhibitors; Female; Mice; Neuropeptide Y; Okadaic Acid; Peptide Fragments; Peptide YY; Serotonin; Serotonin Antagonists; Shellfish Poisoning; Time Factors
PubMed: 34148100
DOI: 10.1007/s00204-021-03095-z -
Sensors (Basel, Switzerland) Apr 2021In the past twenty years marine biotoxin analysis in routine regulatory monitoring has advanced significantly in Europe (EU) and other regions from the use of the mouse... (Review)
Review
In the past twenty years marine biotoxin analysis in routine regulatory monitoring has advanced significantly in Europe (EU) and other regions from the use of the mouse bioassay (MBA) towards the high-end analytical techniques such as high-performance liquid chromatography (HPLC) with tandem mass spectrometry (MS). Previously, acceptance of these advanced methods, in progressing away from the MBA, was hindered by a lack of commercial certified analytical standards for method development and validation. This has now been addressed whereby the availability of a wide range of analytical standards from several companies in the EU, North America and Asia has enhanced the development and validation of methods to the required regulatory standards. However, the cost of the high-end analytical equipment, lengthy procedures and the need for qualified personnel to perform analysis can still be a challenge for routine monitoring laboratories. In developing regions, aquaculture production is increasing and alternative inexpensive Sensitive, Measurable, Accurate and Real-Time (SMART) rapid point-of-site testing (POST) methods suitable for novice end users that can be validated and internationally accepted remain an objective for both regulators and the industry. The range of commercial testing kits on the market for marine toxin analysis remains limited and even more so those meeting the requirements for use in regulatory control. Individual assays include enzyme-linked immunosorbent assays (ELISA) and lateral flow membrane-based immunoassays (LFIA) for EU-regulated toxins, such as okadaic acid (OA) and dinophysistoxins (DTXs), saxitoxin (STX) and its analogues and domoic acid (DA) in the form of three separate tests offering varying costs and benefits for the industry. It can be observed from the literature that not only are developments and improvements ongoing for these assays, but there are also novel assays being developed using upcoming state-of-the-art biosensor technology. This review focuses on both currently available methods and recent advances in innovative methods for marine biotoxin testing and the end-user practicalities that need to be observed. Furthermore, it highlights trends that are influencing assay developments such as multiplexing capabilities and rapid POST, indicating potential detection methods that will shape the future market.
Topics: Animals; Asia; Europe; Marine Toxins; Mice; Okadaic Acid; Saxitoxin
PubMed: 33916687
DOI: 10.3390/s21072499 -
Environmental Science and Pollution... Jan 2024The okadaic acid (OA)-group toxins, including OA, dinophysistoxin-1 (DTX1), dinophysistoxin-2 (DTX2), and dinophysistoxin-3 (DTX3), cause diarrheic shellfish poisoning...
The okadaic acid (OA)-group toxins, including OA, dinophysistoxin-1 (DTX1), dinophysistoxin-2 (DTX2), and dinophysistoxin-3 (DTX3), cause diarrheic shellfish poisoning in humans. To manage OA-group toxins more strictly, Korean regulations were recently revised to consider OA, DTX1, DTX2, and DTX3 combined. Thus, our study characterized the occurrence of OA, DTX1, DTX2, and DTX3 in seafood distributed across South Korea, and a risk assessment of seafood consumption was conducted. Two hundred and seventeen samples from 16 bivalve and 7 non-bivalve species collected from three representative coastal areas in 2021 were analyzed via liquid chromatography-tandem mass spectrometry. OA, DTX1, and DTX3 were detected in 2.3%, 4.1%, and 9.2% of the examined samples, with positive mean levels of 11.3, 16.4, and 40.9 µg/kg, respectively. DTX2 was not detected in any of the samples. At least one OA-group toxin was detected in the bivalve samples, including blood clams, pan shells, hard clams, mussels, and scallops, whereas none were detected in non-bivalves. The estimated acute exposure to OA-group toxins through the intake of seafood in the Korean population and consumer groups was low, ranging from 24.7 to 74.5% of the recommended acute reference dose (ARfD) of 0.33 μg OA equivalents/kg body weight. However, for the scallop consumers aged 7-12 years, acute exposure to OA-group toxins exceeded the ARfD, indicating a possible health risk. These results suggest that including DTX3 in the new regulatory limits is appropriate to protect Korean seafood consumers from exposure to OA-group toxins.
Topics: Animals; Humans; Okadaic Acid; Marine Toxins; Bivalvia; Seafood; Risk Assessment; Pyrans
PubMed: 38147248
DOI: 10.1007/s11356-023-31568-4 -
Marine Drugs Aug 2013Harmful Algal Blooms (HABs) constitute one of the most important sources of contamination in the oceans, producing high concentrations of potentially harmful biotoxins... (Review)
Review
Harmful Algal Blooms (HABs) constitute one of the most important sources of contamination in the oceans, producing high concentrations of potentially harmful biotoxins that are accumulated across the food chains. One such biotoxin, Okadaic Acid (OA), is produced by marine dinoflagellates and subsequently accumulated within the tissues of filtering marine organisms feeding on HABs, rapidly spreading to their predators in the food chain and eventually reaching human consumers causing Diarrhetic Shellfish Poisoning (DSP) syndrome. While numerous studies have thoroughly evaluated the effects of OA in mammals, the attention drawn to marine organisms in this regard has been scarce, even though they constitute primary targets for this biotoxin. With this in mind, the present work aimed to provide a timely and comprehensive insight into the current literature on the effect of OA in marine invertebrates, along with the strategies developed by these organisms to respond to its toxic effect together with the most important methods and techniques used for OA detection and evaluation.
Topics: Animals; Aquatic Organisms; Dinoflagellida; Food Chain; Food Contamination; Harmful Algal Bloom; Humans; Invertebrates; Marine Toxins; Mutagens; Okadaic Acid; Shellfish Poisoning
PubMed: 23939476
DOI: 10.3390/md11082829 -
Ecotoxicology and Environmental Safety Sep 2023Okadaic acid (OA) is one of the most prevalent marine phycotoxin with complex toxicity, which can lead to toxic symptoms such as diarrhea, vomiting, nausea, abdominal...
Okadaic acid (OA) is one of the most prevalent marine phycotoxin with complex toxicity, which can lead to toxic symptoms such as diarrhea, vomiting, nausea, abdominal pain, and gastrointestinal discomfort. Studies have shown that the main affected tissue of OA is digestive tract. However, its toxic mechanism is not yet fully understood. In this study, we investigated the changes that occurred in the epithelial microenvironment following OA exposure, including the epithelial barrier and gut bacteria. We found that impaired epithelial cell junctions, mucus layer destruction, cytoskeletal remodeling, and increased bacterial invasion occurred in colon of rats after OA exposure. At the same time, the gut bacteria decreased in the abundance of beneficial bacteria and increased in the abundance of pathogenic bacteria, and there was a significant negative correlation between the abundance of pathogenic bacteria represented by Escherichia/Shigella and animal body weight. Metagenomic analysis inferred that Escherichia coli and Shigella spp. in Escherichia/Shigella may be involved in the process of cytoskeletal remodeling and mucosal layer damage caused by OA. Although more evidence is needed, our results suggest that opportunistic pathogens may be involved in the complex toxicity of OA during OA-induced epithelial barrier damage.
Topics: Animals; Rats; Okadaic Acid; Body Weight; Colon; Escherichia coli
PubMed: 37597294
DOI: 10.1016/j.ecoenv.2023.115376 -
Experimental Biology and Medicine... Oct 2016The aim of the study was to investigate the influence of hyperphosphorylation of tau induced by okadaic acid on the expression of nicotinic acetylcholine receptors and...
The aim of the study was to investigate the influence of hyperphosphorylation of tau induced by okadaic acid on the expression of nicotinic acetylcholine receptors and the neurotoxicity of β-amyloid peptide. Primary cultures of neurons isolated from the hippocampus of the brains of neonatal rats were exposed to okadaic acid or/and Aβ1-42 Tau phosphorylated at Ser404 and Ser202, and the protein expressions of α7, α4 and α3 nAChR subunits were quantified by Western blotting, and their corresponding mRNAs by real-time PCR. Superoxide dismutase activity was assayed biochemically and malondialdehyde by thiobarbituric acid-reactive substance. As compared to controls, phosphorylations of tau at Ser404 and Ser202 in the neurons were elevated by exposure to 20 nM okadaic acid for 48 h but not by 1 or 2 µM Aβ1-42 Treatment with 20 nM okadaic acid or 1 µM Aβ1-42 for 48 h resulted in the reduced α7, α4 and α3 proteins, and α4 and α3 mRNAs, as well as the decreased activity of superoxide dismutase and the increased malondialdehyde. Okadaic acid and Aβ1-42 together caused more pronounced changes in the expressions of α7 and α4, superoxide dismutase activity and lipid peroxidation than either alone. When pre-treatment with vitamin E or lovastatin, the neurotoxicity induced by okadaic acid was significantly attenuated. These findings indicate that hyperphosphorylation of tau induced by okadaic acid inhibits the expression of nicotinic acetylcholine receptors at both the protein and mRNA levels, as well as enhances the neurotoxicity of β-amyloid peptide.
Topics: Animals; Blotting, Western; Cells, Cultured; Neurons; Okadaic Acid; Phosphorylation; Rats; Rats, Sprague-Dawley; Real-Time Polymerase Chain Reaction; Receptors, Nicotinic; alpha7 Nicotinic Acetylcholine Receptor; tau Proteins
PubMed: 27190248
DOI: 10.1177/1535370216650759 -
Toxins Nov 2018Causative species of Harmful Algal Bloom (HAB) and toxins in commercially exploited molluscan shellfish species are monitored weekly from four classified shellfish...
Causative species of Harmful Algal Bloom (HAB) and toxins in commercially exploited molluscan shellfish species are monitored weekly from four classified shellfish production areas in Perú (three in the north and one in the south). Okadaic acid (OA) and pectenotoxins (PTXs) were detected in hand-picked cells of (-complex and ) and in scallops (), the most important commercial bivalve species in Perú. LC-MS analyses revealed two different toxin profiles associated with species of the -complex: (a) one with OA (0.3⁻8.0 pg cell) and PTX2 (1.5⁻11.1 pg cell) and (b) another with only PTX2 which included populations with different toxin cell quota (9.3⁻9.6 pg cell and 5.8⁻9.2 pg cell). Toxin results suggest the likely presence of two morphotypes of the -complex in the north, and only one of them in the south. Likewise, shellfish toxin analyses revealed the presence of PTX2 in all samples (10.3⁻34.8 µg kg), but OA (7.7⁻15.2 µg kg) only in the northern samples. Toxin levels were below the regulatory limits established for diarrhetic shellfish poisoning (DSP) and PTXs (160 µg OA kg) in Perú, in all samples analyzed. This is the first report confirming the presence of OA and PTX in cells and in shellfish from Peruvian coastal waters.
Topics: Animals; Dinoflagellida; Environmental Monitoring; Food Contamination; Furans; Macrolides; Marine Toxins; Okadaic Acid; Pectinidae; Peru; Pyrans
PubMed: 30477142
DOI: 10.3390/toxins10120490