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.
Highlights
During harmful algae blooms, bivalves accumulate marine toxins, being a serious threat for human consumers of edible shellfish
Metabolic activity assay: Cytotoxic effects of Okadaic acid (OA), dinophysistoxin 1 (DTX1) and dinophysistoxin 2 (DTX2) (1, 10, 20, 40, 100, 200, 500 and 1000 nM) in differentiated Caco-2 cells have been evaluated in a time-dependent manner by the AlamarBlue metabolic activity assay
Caco-2 cells treated with OA, DTX1 or DTX2 did not show any decrease in fluorescence intensity (Figure 2A–C)
Summary
Bivalves accumulate marine toxins, being a serious threat for human consumers of edible shellfish. Toxins causing diarrhetic shellfish poisoning (DSP) are produced by several marine dinoflagellates of the genera, Prorocentrum and Dinophysis, which are of worldwide distribution [1]. DSP is characterized by diarrhea, gastrointestinal distress, nausea, vomiting and, frequently, abdominal pain. These symptoms usually appear from 30 min to 12 h after ingestion of contaminated seafood [2]. As of there have been no records of human fatalities related to acute DSP intoxication [3]. Toxins causing DSP were first reported by Yasumoto et al, in 1978 [2]
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