RT Journal Article T1 Experimental Basis for the High Oral Toxicity of Dinophysistoxin 1: A Comparative Study of DSP A1 Fernández, Diego A. A1 Louzao Ojeda, María del Carmen A1 Fraga, María A1 Vilariño del Río, Natalia A1 Rodríguez Vieytes, Mercedes A1 Botana López, Luis Miguel K1 Okadaic acid K1 Dinophysistoxin-1 K1 Dinophysistoxin-2 K1 Caco-2 K1 Intestinal permeability K1 Trans-epithelial electric resistance K1 Occludin K1 Annexin V K1 Luminex K1 Immunoassay AB 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 PB MDPI YR 2014 FD 2014 LK http://hdl.handle.net/10347/23592 UL http://hdl.handle.net/10347/23592 LA eng NO 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 NO The research leading to these results has received funding from the following FEDER co-funded-grants: from the Ministerio de Ciencia y Tecnología, Spain (AGL2009-13581-CO2-01, AGL2012-40485-CO2-01); from Xunta de Galicia, Spain (10PXIB261254 PR); from the European Union’s Seventh Framework Programme managed by REA [Research Executive Agency; http://ec.europa.eu/research/rea (FP7/2007-2013)] under grant agreement Nos. 211326—CP (CONffIDENCE), 265896 BAMMBO, 265409 µAQUA, 262649 BEADS, 315285 Ciguatools and 312184 PharmaSea; from the Atlantic Area Programme (Interreg IVB Trans-national): 2009-1/117 Pharmatlantic DS Minerva RD 29 abr 2026