Yessotoxin

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Roberto Poletti - One of the best experts on this subject based on the ideXlab platform.

Luis M. Botana - One of the best experts on this subject based on the ideXlab platform.

  • Subacute immunotoxicity of the marine phycotoxin Yessotoxin in rats.
    Toxicon : official journal of the International Society on Toxinology, 2017
    Co-Authors: Sara F. Ferreiro, Natalia Vilarino, Cristina Carrera, M. Carmen Louzao, Germán Santamarina, Antonio González Cantalapiedra, J. Manuel Cifuentes, Andrés C. Vieira, Luis M. Botana
    Abstract:

    Yessotoxin (YTX) is a marine phycotoxin produced by dinoflagellates and accumulated in filter feeding shellfish. YTX content in shellfish is regulated by many food safety authorities to protect human health, although currently no human intoxication episodes have been unequivocally related to YTX presence in food. The immune system has been proposed as one of the target organs of YTX due to alterations of lymphoid tissues and cellular and humoral components. The aim of the present study was to explore subacute immunotoxicity of YTX in rats by evaluating the haematological response, inflammatory cytokine biomarkers and the presence of YTX-induced structural alterations in the spleen and thymus. The results showed that repeated administrations of YTX caused a decrease of lymphocyte percentage and an increase of neutrophil counts, a reduction in interleukine-6 (IL-6) plasmatic levels and histopathological splenic alterations in rats after four intraperitoneal injections of YTX at doses of 50 or 70 μg/kg that were administered every 4 days along a period of 15 days. Therefore, for the first time, subacute YTX-immunotoxicity is reported in rats, suggesting that repeated exposures to low amounts of YTX might also suppose a threat to human health, especially in immuno-compromised populations.

  • Yessotoxin a promising therapeutic tool
    Marine Drugs, 2016
    Co-Authors: Amparo Alfonso, Mercedes R. Vieytes, Luis M. Botana
    Abstract:

    Yessotoxin (YTX) is a polyether compound produced by dinoflagellates and accumulated in filter feeding shellfish. No records about human intoxications induced by this compound have been published, however it is considered a toxin. Modifications in second messenger levels, protein levels, immune cells, cytoskeleton or activation of different cellular death types have been published as consequence of YTX exposure. This review summarizes the main intracellular pathways modulated by YTX and their pharmacological and therapeutic implications.

  • Yessotoxin induces er stress followed by autophagic cell death in glioma cells mediated by mtor and bnip3
    Cellular Signalling, 2014
    Co-Authors: Juan A Rubiolo, Mercedes R. Vieytes, H Lopezalonso, Paulino Martinez, Adrian Millan, Eva Cagide, Felix V Vega, Luis M. Botana
    Abstract:

    Abstract Yessotoxin at nanomolar concentrations can induce programmed cell death in different model systems. Paraptosis-like cell death induced by YTX in BC3H1 cells, which are insensitive to several caspase inhibitors, has also been reported. This makes Yessotoxin of interest in the search of molecules that target cancer cells vulnerabilities when resistance to apoptosis is observed. To better understand the effect of this molecule at the molecular level on tumor cells, we conducted a transcriptomic analysis using 3 human glioma cell lines with different sensitivities to Yessotoxin. We show that the toxin induces a deregulation of the lipid metabolism in glioma cells as a consequence of induction of endoplasmic reticulum stress. The endoplasmic reticulum stress in turn arrests the cell cycle and inhibits the protein synthesis. In the three cell lines used we show that YTX induces autophagy, which is involved in cell death. The sensibility of the cell lines used towards autophagic cell death was related to their doubling time, being the cell line with the lowest proliferation rate the most resistant. The involvement of mTOR and BNIP3 in the autophagy induction was also determined.

  • feasibility of using a surface plasmon resonance based biosensor to detect and quantify Yessotoxin
    Analytica Chimica Acta, 2008
    Co-Authors: Eva S Fonfria, Takeshi Yasumoto, Natalia Vilarino, Mercedes R. Vieytes, Luis M. Botana
    Abstract:

    Abstract Yessotoxin (YTX) is a disulfated polyether toxin produced by marine dinoflagellates. Although there is no clear evidence that YTX is toxic to humans, it is a major cause of false positives in DSP toxin detection by mouse bioassay. We developed a new detection and quantification method for Yessotoxin using a BiaCore X Surface plasmon resonance (SPR)-based biosensor. The assay is based in the interaction of YTX with phosphodiesterase enzymes (PDE), one of its cellular targets. The injection of several YTX concentrations (3–12 μM) over immobilized PDE I, showed a dose dependent binding signal, which K obs (observed rate constant) allowed us to obtain a calibration curve with a linear fit. The detection of Yessotoxin using SPR-based biosensor allows the quantification of the toxin with an automated and repetitive method at concentrations in the range of the 1 mg kg −1 European regulatory limit.

  • phycotoxins chemistry and biochemistry
    2007
    Co-Authors: Luis M. Botana
    Abstract:

    1. Gambierols (Makoto Sasaki, Eva Cagide, and Carmen Louzao). 2. Brevetoxins: Structure, Toxicology and Origin (Ambrose Furey, Keith O'Callaghan, Javier Garcia Fernandez, Mary Lehane, Monica Fernandez Amandi, and Kevin J. James). 3. Chemistry of Maitotoxin (Masayuki Satake). 4. Biochemistry of Maitotoxin (Laura A. de la Rosa, Emilio Alvarez-Parrilla, and Alejandro Martinez). 5. The Chemistry of Palytoxins and Ostreocins (Panagiota Katikou). 6. Biochemistry of Palytoxins and Ostreocins (Carmen Vale and Isabel R. Ares). 7. Chemistry of Cyanobacterial Neurotoxins - Anatoxin-a: Synthetic Approaches (Nuria Armesto Arbella, Keith O'Callaghan, Ambrose Furey, and Kevin J. James). 8. Anatoxin-a and Analogues: Discovery, Distribution and Toxicology (Kevin J. James, Janet Crowley, Mary Lehane, and Ambrose Furey). 9. Pectenotoxins (Christopher Miles). 10. Chemistry, Orgins and Distribution of Yessotoxin and its Analogues (Philipp Hess and John A.B. Aasen). 11. Pharmacology of Yessotoxin (Amparo Alfonso and Carmen Alfonso). 12. Chemistry of Diarrhetic Shellfish Poisoning Toxins (Paulo Vale). 13. The Molecular and Integrative Basis to Domoic Acid Toxicity (John Ramsdell). 14. Hepatotoxic Cyanobacteria (Ana Gago). 15. Polycavernosides (Leo A. Paquette and Mari Yamashita. 16. Structural Assignment and Total Synthesis of Azaspiracid-1 (K.C. Nicolaou, Michael O. Frederick, Kevin P. Cole, Goran Petrovic, and Eriketi Loizidou). 17. Biochemistry of Azaspiracid Poisoning Toxins (Natalia Vilarino). 18. The Cyclic Imines: An Insight into this Emerging Group of Bioactive Marine Toxins (Jordi Molgo and Emmanuelle Girard, and Evelyne Benoit). Index.

Christopher O Miles - One of the best experts on this subject based on the ideXlab platform.

  • effect of mouse strain and gender on ld50 of Yessotoxin
    Toxicon, 2008
    Co-Authors: Tore Aune, Christopher O Miles, John A B Aasen, Stig Larsen
    Abstract:

    Abstract The aim of the present study was to determine whether the intraperitoneal LD 50 for Yessotoxin (YTX) in mice varies with strain or gender. Thirty-six male and 36 female mice, of body weight 16–20 g, from each of the strains ICR (CD-1), Swiss (CFW-1) and NMRI were employed. They were not fasted before YTX treatment. At each dose, nine mice were injected with YTX solutions at 1.0 mL/20 g body weight, and observed for 24 h. Symptoms and time to death were recorded. Within each mouse strain and gender arm, the study was performed as a basic four level Response Surface Pathway designed trial with nine mice at each dose level. YTX was isolated from a culture of Protoceratium reticulatum . The LD 50 values for female and male mice, respectively, were estimated as 380 and 462 μg/kg for the ICR, 269 and 328 μg/kg for the Swiss, and 314 and 412 μg/kg for the NMRI strains. The increases in LD 50 from female to male mice were found to be 22% for ICR, 22% for Swiss and 31% for NMRI. The largest difference in LD 50 among mouse strains was detected between the ICR and Swiss strains, where the deviation was 41% in both females and males. The difference between mouse strains was found significant ( p  = 0.03). For all three strains, females were more susceptible than males, with a difference in LD 50 of 1.2–1.3-fold. The largest difference between the least- and most-susceptible strain was 1.4-fold for both females and males. The largest difference in LD 50 , 1.7-fold, was observed between female Swiss and male ICR mice. The difference between genders was not significant ( p  = 0.12). These results indicate that other factors, like handling of the animals, and the source and handling of the toxin, may significantly influence the outcome of studies on acute toxicity since the reported differences in LD 50 vary by a factor of about seven.

  • convenient large scale purification of Yessotoxin from protoceratium reticulatum culture and isolation of a novel furanoYessotoxin
    Journal of Agricultural and Food Chemistry, 2007
    Co-Authors: Jared I Loader, Veronica Beuzenberg, Lyn R. Briggs, Allan D Hawkes, Dwayne J Jensen, Janine M Cooney, Alistair L Wilkins, Joan M Fitzgerald, Christopher O Miles
    Abstract:

    Yessotoxins from a large-scale culture (226 L) of Protoceratium reticulatum strain CAWD129 were harvested by filtration followed by solid-phase extraction. The extract was purified by column chromatography over basic alumina and reverse-phase flash chromatography to afford pure Yessotoxin (193 mg). Isolation of Yessotoxin was greatly facilitated by selection of a strain which did not produce analogues that interfered with Yessotoxin isolation. In addition to Yessotoxin, numerous minor Yessotoxins were detected by LC-MS in other fractions. From one of these, an early eluting minor analogue with the same molecular weight as Yessotoxin and a similar mass spectrometric fragmentation pattern was isolated. This analogue was identified by NMR and mass spectrometry as a novel Yessotoxin analogue containing a furan ring in the side chain. This finding reveals biosynthetic flexibility of the Yessotoxin pathway in P. reticulatum and confirms earlier findings of production of many minor Yessotoxin analogues by this a...

  • isolation of Yessotoxin 32 o β l arabinofuranosyl 5 1 β l arabinofuranoside from protoceratium reticulatum
    Toxicon, 2006
    Co-Authors: Christopher O Miles, Veronica Beuzenberg, Allan D Hawkes, Dwayne J Jensen, Janine M Cooney, Alistair L Wilkins, Andrew I Selwood, Lincoln A Mackenzie
    Abstract:

    Yessotoxin 32-O-[β-l-arabinofuranosyl-(5′→1″)-β-l-arabinofuranoside] (3) was isolated from extracts of Protoceratium reticulatum during a large scale isolation of Yessotoxin (1). The structure was characterized by mass spectrometry and NMR spectroscopy. Di-glycoside-3, along with the corresponding mono-glycoside (2) were detected in cultures of P. reticulatum originating from Europe and New Zealand, suggesting that production of arabinosides of 1 is a normal feature of this alga. Formation of multiply charged anions and fragmentation of 3 occurred much more readily than for 1 and 2 under the LC-MS conditions used in this study.

  • evidence for numerous analogs of Yessotoxin in protoceratium reticulatum
    Harmful Algae, 2005
    Co-Authors: Christopher O Miles, Dwayne J Jensen, Alistair L Wilkins, Ingunn A Samdal, John Aasen, Michael A Quilliam, Dirk Petersen, Lyn M Briggs, Frode Rise, Janine M Cooney
    Abstract:

    A solid-phase extract from Protoceratium reticulatum was partitioned between water and butanol and the two fractions purified on an alumina column. Fractionation was monitored by ELISA and LC–MS. Results indicate that while almost all Yessotoxin (1) was extracted into butanol, large amounts of Yessotoxin analogs remained in the aqueous extract along with lesser amounts in the butanolic extract. NMR analysis of selected fractions from reverse-phase chromatography of the extracts confirmed the presence of Yessotoxin analogs, although structure determinations were not possible due to the complexity of the mixtures. Analysis of fractions with LC–MS3 and neutral-loss LC–MS/MS indicated the presence of more than 90 Yessotoxin analogs, although structures for most of these have not yet been determined. These analogs provide a mechanism to rationalise the discrepancy between ELISA and LC–MS analyses of algae and shellfish.

  • Yessotoxins in norwegian blue mussels mytilus edulis uptake from protoceratium reticulatum metabolism and depuration
    Toxicon, 2005
    Co-Authors: John A B Aasen, Lyn R. Briggs, Christopher O Miles, Ingunn A Samdal, Einar Dahl, Tore Aune
    Abstract:

    Abstract The Protoceratium reticulatum cell density at Flodevigen reached a maximum of 2200 cells/L on 16 May 2001. The levels of Yessotoxins (YTXs) in blue mussels ( Mytilus edulis ) at the same site increased sharply by 14 May and peaked on 28 May, after which they steadily declined. No other algal species present showed a similar pattern of correspondence. Together with the recent finding that Norwegian strains of P. reticulatum produce YTXs, these results indicate that P. reticulatum causes Yessotoxin (YTX) contamination of shellfish in Norway, and that only relatively low cell densities are necessary for this to occur. The mussels from Flodevigen were analyzed by LC-MS for YTX, 45-hydroxyYTX, carboxyYTX, and a new Yessotoxin believed to be 45-hydroxycarboxyYTX, and by ELISA for YTXs. The seasonal variations in toxin content versus time measured by the two methods were qualitatively very similar, although the response in the ELISA was 3–9 times higher due to the antibodies detecting other YTXs that were not detected by the LC-MS method. Changes in the LC-MS profile for YTXs, and in the ratio of YTXs by LC-MS to YTXs by ELISA with time, were consistent with extensive metabolism of YTX in the mussels. Kinetic analysis of the LC-MS data showed an initial half-life of 20 days for YTX, and for YTX+45-hydroxyYTX, in the mussels. Similar analysis of the ELISA data gave a half-life of 24 days for YTXs. The depuration rate remained consistent over a 3-month period during which the temperature remained at 13–16 °C.

Masayuki Satake - One of the best experts on this subject based on the ideXlab platform.

Patrizia Ciminiello - One of the best experts on this subject based on the ideXlab platform.