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Toxicon : Official Journal of the... Mar 2019Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after... (Review)
Review
Okadaic acid (OA), a potent polyether marine toxin, accumulates in the digestive glands of marine mollusks and therefore can severely threaten the health of humans after ingestion of contaminated shellfish. In vivo and in vitro studies have revealed that exposure of various cells, including human embryonic amniotic cells, hepatocytes, neuroblastoma cells, to OA induces morphological and functional modifications as well as the death of cells. As the number of reports on OA poisoning has increased, this toxin has gradually attracted the public's attention, and researchers are trying to study it. This review summarizes the current literature on the toxicity effects of OA, in addition to its detection and detoxification.
Topics: Animals; Dinoflagellida; Humans; Inactivation, Metabolic; Marine Toxins; Mollusca; Okadaic Acid; Shellfish Poisoning
PubMed: 30639658
DOI: 10.1016/j.toxicon.2018.12.007 -
Neural Regeneration Research Sep 2018Despite the many years of extensive research using rodent models to study Alzheimer's disease (AD), no cure or disease halting drug exists. An increasing number of... (Review)
Review
Despite the many years of extensive research using rodent models to study Alzheimer's disease (AD), no cure or disease halting drug exists. An increasing number of people are suffering from the disease and a therapeutic intervention is needed. Therefore, it is necessary to have complementary models to aid in the drug discovery. The zebrafish animal model is emerging as a valuable model for the investigation of AD and neurodegenerative drug discovery. The main genes involved in human AD have homologous counterparts in zebrafish and have conserved function. The basic brain structure of the zebrafish is also conserved when compared to the mammalian brain. Recently an AD model was established by administering okadaic acid to zebrafish. It was used to test the efficacy of a novel drug, lanthionine ketimine-5-ethyl ester, and to elucidate its mechanism of action. This demonstrated the ability of the okadaic acid-induced AD zebrafish model to be implemented in the drug discovery process for therapeutics against AD.
PubMed: 30127109
DOI: 10.4103/1673-5374.237111 -
Toxins Jul 2019Several planktonic dinoflagellate species of the genus produce one or two groups of lipophilic toxins: (i) okadaic acid (OA) and its derivatives, the dinophysistoxins...
Several planktonic dinoflagellate species of the genus produce one or two groups of lipophilic toxins: (i) okadaic acid (OA) and its derivatives, the dinophysistoxins (DTXs), and (ii) pectenotoxins (PTXs) [...].
Topics: Animals; Biological Monitoring; Dinoflagellida; Food Contamination; Humans; Marine Toxins; Okadaic Acid; Pyrans; Shellfish
PubMed: 31315196
DOI: 10.3390/toxins11070413 -
Current Medicinal Chemistry 2021Many natural products with extraordinary chemical structures and brilliant biological activities have been obtained from marine organisms. We have investigated such... (Review)
Review
Many natural products with extraordinary chemical structures and brilliant biological activities have been obtained from marine organisms. We have investigated such fascinating bioactive molecules, exemplified by the potent marine toxin palytoxin and the antitumor molecule halichondrin B, which has been developed as the anticancer drug Halaven®, to explore novel frontiers in organic chemistry and bioscience. Working within the traditional discipline, we have sought to acquire a deeper understanding of biological phenomena. We introduce here our major work along with up-todate topics. We isolated yoshinone A from marine cyanobacteria and completed a gram-scale synthesis. Yoshinone A is a novel polyketide that inhibited the differentiation of 3T3-L1 cells into adipocytes without significant cytotoxicity. The detailed mechanisms of action will be elucidated via further experiments in vitro and in vivo. In this study, we explore the true producers of okadaic acid and halichondrin B by immunostaining of Halichondria okadai with an antibody that was prepared using these natural products as an antigen. We will analyze isolated symbionts and reveal biosynthetic pathways.
Topics: 3T3-L1 Cells; Animals; Aquatic Organisms; Biological Products; Cyanobacteria; Ethers, Cyclic; Japan; Macrolides; Mice; Okadaic Acid; Polyketides; Pyrones
PubMed: 31642409
DOI: 10.2174/0929867326666191022125851 -
Organic Letters Jul 2023After a recent total synthesis had resolved all issues surrounding the constitution and stereostructure of prorocentin, it was possible to devise a new approach aiming...
After a recent total synthesis had resolved all issues surrounding the constitution and stereostructure of prorocentin, it was possible to devise a new approach aiming at an improved supply of this scarce marine natural product; this compound is a cometabolite of the prototypical phosphatase inhibitor okadaic acid but still awaits detailed biological profiling. The revised entry starts from 2-deoxy-d-glucose; keys to success were a telescoped hemiacetal reduction/acetal cleavage and an exquisitely selective gold/Brønsted acid-cocatalyzed spiroacetalization.
Topics: Okadaic Acid; Enzyme Inhibitors; Furans; Acetals
PubMed: 37358405
DOI: 10.1021/acs.orglett.3c01720 -
Toxicology May 2022Okadaic acid (OA, C₄₄H₆₈O₁₃) is a neurotoxin and phosphatase inhibitor produced by several dinoflagellate species. OA is widely known to accumulate in black...
Okadaic acid (OA, C₄₄H₆₈O₁₃) is a neurotoxin and phosphatase inhibitor produced by several dinoflagellate species. OA is widely known to accumulate in black sponges and is associated with seafood poisoning. Humans can be exposed to OA by consuming contaminated shellfish that have accumulated toxins during algal blooms. Evidence from in vitro and in vivo studies demonstrate that OA exposure causes neurotoxicity in addition to diarrheal syndrome. It is unclear whether exposure to OA affects retinal function, a part of the central nervous system. We evaluated the toxicity of OA in human retinal pigment epithelial cells (ARPE-19) and in zebrafish retinas. Cell-based assays determined that OA significantly decreased cell viability in a dose-dependent manner and increased oxidative stress, inflammation and cell death compared to the untreated control group. In the in vivo study, zebrafish embryos at 24 h post fertilization (hpf) were treated with/without OA for four days, endpoint measurements including mortality, malformations, delayed hatching, altered heartbeat and reduced movement were performed. OA exposure increased mortality, decreased hatching, heartbeat rate, and caused morphological abnormalities. OA exposure also markedly decreased the expression of antioxidant genes and a significantly increased inflammation as well as evoking a loss of photoreceptors in zebrafish embryos. The data suggest that consuming OA-contaminated seafood can induce retinal toxicity.
Topics: Animals; Humans; Inflammation; Okadaic Acid; Oxidative Stress; Retina; Zebrafish
PubMed: 35577138
DOI: 10.1016/j.tox.2022.153209 -
Journal of Cancer Research and Clinical... Sep 2023Okadaic acid class of tumor promoters are transformed into endogenous protein inhibitors of PP2A, SET, and CIP2A in human cancers. This indicates that inhibition of PP2A... (Review)
Review
PURPOSE
Okadaic acid class of tumor promoters are transformed into endogenous protein inhibitors of PP2A, SET, and CIP2A in human cancers. This indicates that inhibition of PP2A activity is a common mechanism of cancer progression in humans. It is important to study the roles of SET and CIP2A vis-à-vis their clinical significance on the basis of new information gathered from a search of PubMed.
RESULTS AND DISCUSSION
The first part of this review introduces the carcinogenic roles of TNF-α and IL-1, which are induced by the okadaic acid class of compounds. The second part describes unique features of SET and CIP2A in cancer progression for several types of human cancer: (1) SET-expressing circulating tumor cells (SET-CTCs) in breast cancer, (2) knockdown of CIP2A and increased PP2A activity in chronic myeloid leukemia, (3) CIP2A and epidermal growth factor receptor (EGFR) activity in erlotinib sensitive- and resistant-non-small cell lung cancer, (4) SET antagonist EMQA plus radiation therapy against hepatocellular carcinoma, (5) PP2A inactivation as a common event in colorectal cancer, (6) prostate cancer susceptibility variants, homeobox transcription factor (HOXB13 T) and CIP2A T, and (7) SET inhibitor OP449 for pre-clinical investigation of pancreatic cancer. In the Discussion, the binding complex of SET is briefly introduced, and overexpression of SET and CIP2A proteins is discussed in relation to age-associated chronic inflammation (inflammaging).
CONCLUSION
This review establishes the concept that inhibition of PP2A activity is a common mechanism of human cancer progression and activation of PP2A activity leads to effective anticancer therapy.
Topics: Male; Humans; Okadaic Acid; Carcinoma, Non-Small-Cell Lung; Carcinogens; Lung Neoplasms; Membrane Proteins; Cell Line, Tumor; Intracellular Signaling Peptides and Proteins; Liver Neoplasms; Autoantigens
PubMed: 37097392
DOI: 10.1007/s00432-023-04800-4 -
Marine Drugs Oct 2015Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of... (Review)
Review
Okadaic acid (OA) and microcystin (MC) as well as several other microbial toxins like nodularin and calyculinA are known as tumor promoters as well as inducers of apoptotic cell death. Their intracellular targets are the major serine/threonine protein phosphatases. This review summarizes mechanisms believed to be responsible for the death induction and tumor promotion with focus on the interdependent production of reactive oxygen species (ROS) and activation of Ca(2+)/calmodulin kinase II (CaM-KII). New data are presented using inhibitors of specific ROS producing enzymes to curb nodularin/MC-induced liver cell (hepatocyte) death. They indicate that enzymes of the arachidonic acid pathway, notably phospholipase A2, 5-lipoxygenase, and cyclooxygenases, may be required for nodularin/MC-induced (and presumably OA-induced) cell death, suggesting new ways to overcome at least some aspects of OA and MC toxicity.
Topics: Animals; Apoptosis; Carcinogens; Cell Death; Enzyme Inhibitors; Humans; Marine Toxins; Microcystins; Okadaic Acid; Oxazoles; Peptides, Cyclic; Phosphoprotein Phosphatases; Reactive Oxygen Species
PubMed: 26506362
DOI: 10.3390/md13106505 -
Marine Drugs Aug 2022Okadaic acid (OA) is a marine biotoxin associated with diarrhetic shellfish poisoning (DSP), posing some threat to human beings. The oral toxicity of OA is complex, and...
Okadaic acid (OA) is a marine biotoxin associated with diarrhetic shellfish poisoning (DSP), posing some threat to human beings. The oral toxicity of OA is complex, and the mechanism of toxicity is not clear. The interaction between OA and gut microbiota may provide a reasonable explanation for the complex toxicity of OA. Due to the complex environment in vivo, an in vitro study may be better for the interactions between OA and gut microbiome. Here, we conducted an in vitro fermentation experiment of gut bacteria in the presence of 0-1000 nM OA. The remolding ability of OA on bacterial composition was investigated by 16S rDNA sequencing, and differential metabolites in fermentation system with different concentration of OA was detected by LC-MS/MS. We found that OA inhibited some specific bacterial genera but promoted others. In addition, eight possible metabolites of OA, including dinophysistoxin-2 (DTX-2), were detected in the fermentation system. The abundance of was strongly correlated with the possible metabolites of OA, suggesting that may be involved in the metabolism of OA in vitro. Our findings confirmed the direct interaction between OA and gut bacteria, which helps to reveal the metabolic process of OA and provide valuable evidence for elucidating the complex toxicity of OA.
Topics: Animals; Chromatography, Liquid; DNA, Ribosomal; Gastrointestinal Microbiome; Humans; Marine Toxins; Okadaic Acid; Pyrans; Rats; Tandem Mass Spectrometry
PubMed: 36135745
DOI: 10.3390/md20090556 -
Harmful Algae May 2024This article presents the first results on shellfish toxicity in the Slovenian sea (Gulf of Trieste, Adriatic Sea) since the analytical methods for the detection of...
Okadaic acid as a major problem for the seafood safety (Mytilus galloprovincialis) and the dynamics of toxic phytoplankton in the Slovenian coastal sea (Gulf of Trieste, Adriatic Sea).
This article presents the first results on shellfish toxicity in the Slovenian sea (Gulf of Trieste, Adriatic Sea) since the analytical methods for the detection of biotoxins (PSP, ASP, DSP and other lipophilic toxins) in bivalve molluscs were included in the national monitoring program in 2013. In addition to toxins, the composition and abundance of toxic phytoplankton and general environmental characteristics of the seawater (surface temperature and salinity) were also monitored. During the 2014-2019 study period, only lipophilic toxins were detected (78 positive tests out of 446 runs), of which okadaic acid (OA) predominated in 97 % of cases, while dinophysistoxin-2 and yessotoxins only gave a positive result in one sampling event each. The number of samples that did not comply with the EC Regulation for the OA group was 17 or 3.8 % of all tests performed, all of which took place from September to November, while a few positive OA tests were also recorded in December, April, and May. This toxicity pattern was consistent with the occurrence pattern of the five most common DSP-producing dinoflagellates, which was supported by the development of warm and thermohaline stratified waters: Dinophysis caudata, D. fortii, D. sacculus, D. tripos and Phalacroma rotundatum. The strong correlation (r = 0.611, p < 0.001) between D. fortii, reaching abundances of up to 950 cells L, and OA suggests that D. fortii is the main cause of OA production in Slovenian waters. Strong interannual variations in OA and phytoplankton dynamics, exacerbated by the effects of anthropogenic impacts in this coastal ecosystem, reduce the predictability of toxicity events and require continuous and efficient monitoring. Our results also show that the introduction of the LC-MS/MS method for lipophilic toxins has improved the management of aquaculture activities, which was not as accurate based on mouse bioassays.
Topics: Okadaic Acid; Animals; Phytoplankton; Marine Toxins; Slovenia; Mytilus; Seafood; Seawater; Dinoflagellida
PubMed: 38830710
DOI: 10.1016/j.hal.2024.102632