-
Marine Drugs Dec 2020Okadaic acid (OA) group toxins may accumulate in shellfish and can result in diarrhetic shellfish poisoning when consumed by humans, and are therefore regulated....
Okadaic acid (OA) group toxins may accumulate in shellfish and can result in diarrhetic shellfish poisoning when consumed by humans, and are therefore regulated. Purified toxins are required for the production of certified reference materials used to accurately quantitate toxin levels in shellfish and water samples, and for other research purposes. An improved procedure was developed for the isolation of dinophysistoxin-2 (DTX2) from shellfish (), reducing the number of purification steps from eight to five, thereby increasing recoveries to ~68%, compared to ~40% in a previously reported method, and a purity of >95%. Cell densities and toxin production were monitored in cultures of , that produced OA, DTX1, and their esters, over ~1.5 years with maximum cell densities of ~70,000 cells mL observed. Toxin accumulation progressively increased over the study period, to ~0.7 and 2.1 mg L of OA and DTX1 (including their esters), respectively, providing information on appropriate harvesting times. A procedure for the purification of OA and DTX1 from the harvested biomass was developed employing four purification steps, with recoveries of ~76% and purities of >95% being achieved. Purities were confirmed by LC-HRMS, LC-UV, and NMR spectroscopy. Additional stability observations led to a better understanding of the chemistry of these toxins.
Topics: Animals; Biomass; Chromatography, High Pressure Liquid; Magnetic Resonance Spectroscopy; Marine Toxins; Microalgae; Mytilus edulis; Okadaic Acid; Spectrophotometry, Ultraviolet; Tandem Mass Spectrometry
PubMed: 33339248
DOI: 10.3390/md18120647 -
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 -
Fertility and Sterility Aug 2009To investigate the effects of nicotine in combination with okadaic acid (OA) or taxol on bovine oocyte maturation and subsequent embryonic development.
OBJECTIVE
To investigate the effects of nicotine in combination with okadaic acid (OA) or taxol on bovine oocyte maturation and subsequent embryonic development.
DESIGN
Prospective randomized study.
SETTING
University research laboratory.
PATIENT(S)
Bovine ovaries, oocytes, and embryos.
INTERVENTION(S)
Oocyte maturation and subsequent embryo development in the presence of nicotine in combination with okadaic acid and taxol.
MAIN OUTCOME MEASURE(S)
Haploid composition, cleavage rate, IVF and parthenogenetic embryo development, blastocyst cell number.
RESULT(S)
The results showed that nicotine and OA or nicotine and taxol significantly decreased oocyte maturation rates. Combinations of nicotine (10 or 50 micromol/L) and OA (0.01 or 0.05 micromol/L) did not affect oocyte haploid composition; however, taxol alone or combined with nicotine caused a decrease in haploid composition compared with control. Parthenogenetic activation of oocytes that were matured in nicotine, OA, or taxol resulted in blastocyst development rates of 12%-17%, which were not different from the control. Various combinations of nicotine and OA or nicotine and taxol significantly lowered (3%-8%) blastocyst development compared with control. The average cell number of blastocysts derived from nicotine + OA- and nicotine + taxol-treated oocytes was lower than all other treatment groups and control. For oocytes fertilized in vitro, oocytes matured in OA, taxol, or combinations of nicotine and OA or taxol-containing media resulted in significantly lower cleavage rates and blastocyst development compared with the control group and the 10 micromol/L nicotine treatment group. The IVF embryos cultured in nicotine + OA-containing medium had a significantly lower blastocyst development rate.
CONCLUSION(S)
Combinations of nicotine with OA or taxol adversely affect oocyte maturation and subsequently result in poor blastocyst development.
Topics: Animals; Cattle; Cells, Cultured; Dose-Response Relationship, Drug; Drug Synergism; Embryonic Development; Female; Nicotine; Okadaic Acid; Oocytes; Paclitaxel
PubMed: 18793772
DOI: 10.1016/j.fertnstert.2008.07.1702 -
Toxins Nov 2013In 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...
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.
Topics: Administration, Oral; Animals; Antioxidants; Diarrhea; Feces; Female; Gene Expression; Immunohistochemistry; Inactivation, Metabolic; Intestine, Small; Kidney; Liver; Mice; Okadaic Acid; Oxidative Stress; Stomach
PubMed: 24217398
DOI: 10.3390/toxins5112093 -
Brain Research Nov 2010Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes cognitive and behavioral deterioration in the elderly. Neurofibrillary tangles (NFTs) are...
Alzheimer's disease (AD) is a progressive neurodegenerative disease that causes cognitive and behavioral deterioration in the elderly. Neurofibrillary tangles (NFTs) are one of the pathological hallmarks of AD that has been shown to correlate positively with the severity of dementia in the neocortex of AD patients. In an attempt to characterize an in vivo AD tauopathy model, okadaic acid (OA), a protein phosphatase inhibitor, was microinfused into the right lateral dorsal hippocampus area of ovariectomized adult rat. Cognitive deficiency was seen in OA-treated rats without a change in motor function. Both silver staining and immunohistochemistry staining revealed that OA treatment induces NFTs-like conformational changes in both the cortex and hippocampus. Phosphorylated tau as well as cyclin-dependent kinase 5 (cdk5) and its coactivator, p25, were significantly increased in these regions of the brain. Oxidative stress was also increased with OA treatment as measured by protein carbonylation and lipid peroxidation. These data suggest that the unilateral microinfusion of OA into the dorsal hippocampus causes cognitive deficiency, NFTs-like pathological changes, and oxidative stress as seen in AD pathology via tau hyperphosphorylation caused by inhibition of protein phosphatases.
Topics: Alzheimer Disease; Animals; Blotting, Western; Brain; Cognition Disorders; Disease Models, Animal; Enzyme Inhibitors; Female; Immunohistochemistry; Injections, Intraventricular; Maze Learning; Neurofibrillary Tangles; Okadaic Acid; Ovariectomy; Oxidative Stress; Phosphorylation; Rats; Rats, Sprague-Dawley; Tauopathies
PubMed: 20807517
DOI: 10.1016/j.brainres.2010.08.077 -
Food Additives & Contaminants. Part A,... Jun 2010Okadaic acid, a diarrhetic shellfish poison, domoic acid, an amnesic shellfish poison, and saxitoxin, a paralytic shellfish poison, are three of the best-known marine...
Okadaic acid, a diarrhetic shellfish poison, domoic acid, an amnesic shellfish poison, and saxitoxin, a paralytic shellfish poison, are three of the best-known marine biotoxins. The mouse bioassay is the method most widely used to detect many of these toxins in shellfish samples, but animal welfare concerns have prompted researchers to seek alternative methods of detection. In this study, three direct competitive enzyme-linked immunosorbent assays (ELISAs), each based on antibodies raised in rabbits against a conjugate of the analyte of interest, were developed for marine biotoxin detection in mussel, oyster, and scallop. One assay was for okadaic acid, one for saxitoxin, and one for domoic acid usually detected and quantified by high-performance liquid chromatography-ultraviolet light (HPLC-UV). All three compounds and a number of related toxins were extracted quickly and simply from the shellfish matrices with a 9 : 1 mixture of ethanol and water before analysis. The detection capabilities (CCbeta values) of the developed ELISAs were 150 microg kg(-1) for okadaic acid, 50 microg kg(-1) for domoic acid, and 5 microg kg(-1) or less for saxitoxin. The assays proved satisfactory when used over a 4-month period for the analysis of 110 real samples collected in Belgium.
Topics: Animals; Antibody Specificity; Belgium; Bivalvia; Calibration; Carcinogens; Chromatography, High Pressure Liquid; Enzyme-Linked Immunosorbent Assay; Kainic Acid; Marine Toxins; Mice; Okadaic Acid; Ostreidae; Pectinidae; Rabbits; Saxitoxin; Sensitivity and Specificity
PubMed: 20486002
DOI: 10.1080/19440041003662881 -
Toxins Aug 2018Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by... (Review)
Review
Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.
Topics: Acrylamides; Animals; Humans; Marine Toxins; Okadaic Acid; Shellfish Poisoning; Spiro Compounds
PubMed: 30096904
DOI: 10.3390/toxins10080324 -
Marine Drugs Feb 2023Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common...
Marine toxins (MTs) are a group of structurally complex natural products with unique toxicological and pharmacological activities. In the present study, two common shellfish toxins, okadaic acid (OA) () and OA methyl ester (), were isolated from the cultured microalgae strain PL11. OA can significantly activate the latent HIV but has severe toxicity. To obtain more tolerable and potent latency reversing agents (LRAs), we conducted the structural modification of OA by esterification, yielding one known compound () and four new derivatives (-). Flow cytometry-based HIV latency reversal activity screening showed that compound possessed a stronger activity (EC = 46 ± 13.5 nM) but was less cytotoxic than OA. The preliminary structure-activity relationships (SARs) indicated that the carboxyl group in OA was essential for activity, while the esterification of carboxyl or free hydroxyls were beneficial for reducing cytotoxicity. A mechanistic study revealed that compound promotes the dissociation of P-TEFb from the 7SK snRNP complex to reactivate latent HIV-1. Our study provides significant clues for OA-based HIV LRA discovery.
Topics: Humans; Okadaic Acid; HIV Infections; Virus Latency; HIV-1; Marine Toxins; Dinoflagellida
PubMed: 36976207
DOI: 10.3390/md21030158 -
Journal of Occupational Health Nov 2016In the present study an attempt was made to estimate coefficients of dose response curves for PCC aberrations induced by CalyculinA and Okadaic acid, using Co gamma...
OBJECTIVE
In the present study an attempt was made to estimate coefficients of dose response curves for PCC aberrations induced by CalyculinA and Okadaic acid, using Co gamma radiation and 8 MeV pulsed electron beam for biodosimetry application.
MATERIALS AND METHODS
The modified method outlined by Puig et al. 2013 was used to conduct Calyculin A and Okadaic acid induced PCC assay in human blood lymphocytes.Chemical treatment was given for the last 1 h of a 48 h culture. The study was carried out in the dose range 2.5 to 20 Gy using Co gamma rays and 8 MeV pulsed electron beam.
RESULTS AND CONCLUSIONS
Results show a linear dose dependent increase with a slope of 0.047 ± 0.001 from Calycalin A PCC and 0.048 ± 0.002 form Okadaic acid PCC. The slope of the fragments curve was 0.327 ± 0.006 from Calyculin A and 0.328 ± 0.006 from Okadaic acid PCC. Further, dose calibration studies were carried out for 8 MeV electron using Calyculin A PCC assay and the obtained slope from ring yield was 0.054 ± 0.002 and 0.427 ± 0.009 from fragment yield.
Topics: Carcinogens; Chromosome Aberrations; Dose-Response Relationship, Drug; Humans; Lymphocytes; Marine Toxins; Okadaic Acid; Oxazoles; Radiometry
PubMed: 27725377
DOI: 10.1539/joh.16-0049-OA -
Toxins Mar 2020Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of...
Diarrhetic shellfish poisoning (DSP) is a syndrome caused by the intake of shellfish contaminated with a group of lipophilic and thermostable toxins, which consists of okadaic acid (OA), dinophysistoxin-1 (DTX-1) and dinophysistoxin-2 (DTX-2). These toxins are potent protein Ser/Thr phosphatase inhibitors, mainly type 1 protein phosphatase (PP1) and type 2A protein phosphatase (PP2A). Different effects have been reported at the cellular, molecular and genetic levels. In this study, changes in cell survival and cell mobility induced by OA, DTX-1 and DTX-2 were determined in epithelial cell lines of the colon and colon cancer. The cell viability results showed that tumoral cell lines were more resistant to toxins than the nontumoral cell line. The results of the functional assays for testing cell migration, evaluation of cell death and the expression of proteins associated with cell adhesion showed a dual effect of toxins since in the nontumoral cell line, a greater induction of cell death, presumably by anoikis, was detected. In the tumoral cell lines, there was an induction of a more aggressive phenotype characterized by increased resistance to toxins, increased migration and increased FAK activation. In tumoral cell lines of colon cancer, OA, DTX-1/DTX-2 induce a more aggressive phenotype.
Topics: Animals; Carcinogens; Cell Line, Tumor; Cell Movement; Cell Proliferation; Cell Survival; Colonic Neoplasms; Focal Adhesion Kinase 1; Humans; Inhibitory Concentration 50; Okadaic Acid; Protein Phosphatase 2
PubMed: 32183214
DOI: 10.3390/toxins12030179