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Combined cytotoxicity of the phycotoxin okadaic acid and mycotoxins on intestinal and neuroblastoma human cell models

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Hayashi, A ORCID: 0000-0002-7348-9682, Dorantes-Aranda, JJ ORCID: 0000-0003-1513-6501, Bowman, JP ORCID: 0000-0002-4528-9333 and Hallegraeff, G ORCID: 0000-0001-8464-7343 2018 , 'Combined cytotoxicity of the phycotoxin okadaic acid and mycotoxins on intestinal and neuroblastoma human cell models' , Toxins, vol. 10, no. 12 , pp. 1-14 , doi: 10.3390/toxins10120526.

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Abstract

Mycotoxins are emerging toxins in the marine environment, which can co-occur withalgal toxins to exert synergistic or antagonistic effects for human seafood consumption. The currentstudy assesses the cytotoxicity of the algal toxin okadaic acid, shellfish, and dust storm-associatedmycotoxins alone or in combination on human intestinal (HT-29) and neuroblastoma (SH-SY5Y)cell lines. Based on calculated IC50 (inhibitory concentration 50%) values, mycotoxins and thealgal toxin on their own exhibited increased cytotoxicity in the order of sydowinin A < sydowininB << patulin < alamethicin < sydowinol << gliotoxin = okadaic acid against the HT-29 cell line, andsydowinin B < sydowinin A << alamethicin = sydowinol < patulin, << gliotoxin < okadaic acidagainst the SH-SY5Y cell line. Combinations of okadaic acid–sydowinin A, –alamethicin, –patulin, and–gliotoxin exhibited antagonistic effects at low-moderate cytotoxicity, but became synergistic at highcytotoxicity, while okadaic acid–sydowinol displayed an antagonistic relationship against HT-29 cells.Furthermore, only okadaic acid–sydowinin A showed synergism, while okadaic acid–sydowinol,–alamethicin, –patulin, and –gliotoxin combinations demonstrated antagonism against SH-SY5Y.While diarrhetic shellfish poisoning (DSP) from okadaic acid and analogues in many parts of theworld is considered to be a comparatively minor seafood toxin syndrome, our human cell modelstudies suggest that synergisms with certain mycotoxins may aggravate human health impacts,depending on the concentrations. These findings highlight the issues of the shortcomings of currentregulatory approaches, which do not regulate for mycotoxins in shellfish and treat seafood toxins asif they occur as single toxins.

Item Type: Article
Authors/Creators:Hayashi, A and Dorantes-Aranda, JJ and Bowman, JP and Hallegraeff, G
Keywords: okadaic acid, sydowinin A, sydowinol, alamethicin, patulin, gliotoxin, combination index, synergy
Journal or Publication Title: Toxins
Publisher: MDPIAG
ISSN: 2072-6651
DOI / ID Number: 10.3390/toxins10120526
Copyright Information:

Copyright 2018 The Authors. Licensed under Creative Commons Attribution 4.0 International (CC BY 4.0) https://creativecommons.org/licenses/by/4.0/

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