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Toxins 2014, 6(1), 211-228; doi:10.3390/toxins6010211
Article

Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP

1
, 1,* , 1
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Received: 31 October 2013; in revised form: 23 December 2013 / Accepted: 28 December 2013 / Published: 3 January 2014
(This article belongs to the collection Marine and Freshwater Toxins)
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Abstract: Okadaic acid (OA) and its analogues, dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2), are lipophilic and heat-stable marine toxins produced by dinoflagellates, which can accumulate in filter-feeding bivalves. These toxins cause diarrheic shellfish poisoning (DSP) in humans shortly after the ingestion of contaminated seafood. Studies carried out in mice indicated that DSP poisonous are toxic towards experimental animals with a lethal oral dose 2–10 times higher than the intraperitoneal (i.p.) lethal dose. The focus of this work was to study the absorption of OA, DTX1 and DTX2 through the human gut barrier using differentiated Caco-2 cells. Furthermore, we compared cytotoxicity parameters. Our data revealed that cellular viability was not compromised by toxin concentrations up to 1 μM for 72 h. Okadaic acid and DTX2 induced no significant damage; nevertheless, DTX1 was able to disrupt the integrity of Caco-2 monolayers at concentrations above 50 nM. In addition, confocal microscopy imaging confirmed that the tight-junction protein, occludin, was affected by DTX1. Permeability assays revealed that only DTX1 was able to significantly cross the intestinal epithelium at concentrations above 100 nM. These data suggest a higher oral toxicity of DTX1 compared to OA and DTX2.
Keywords: okadaic acid; dinophysistoxin-1; dinophysistoxin-2; Caco-2; intestinal permeability; trans-epithelial electric resistance; occludin; annexin V; Luminex; immunoassay okadaic acid; dinophysistoxin-1; dinophysistoxin-2; Caco-2; intestinal permeability; trans-epithelial electric resistance; occludin; annexin V; Luminex; immunoassay
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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MDPI and ACS Style

Fernández, D.A.; Louzao, M.C.; Fraga, M.; Vilariño, N.; Vieytes, M.R.; Botana, L.M. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP. Toxins 2014, 6, 211-228.

AMA Style

Fernández DA, Louzao MC, Fraga M, Vilariño N, Vieytes MR, Botana LM. Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP. Toxins. 2014; 6(1):211-228.

Chicago/Turabian Style

Fernández, Diego A.; Louzao, M. C.; Fraga, María; Vilariño, Natalia; Vieytes, Mercedes R.; Botana, Luis M. 2014. "Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP." Toxins 6, no. 1: 211-228.


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