Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models

Ferron, Pierre-Jean; Dumazeau, Kevin; Beaulieu, Jean‐François; Hégarat, Ludovic Le; Fessard, Valérie

doi:10.3390/toxins8020050

Cited by 22 publications

(13 citation statements)

References 53 publications

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“…However, differentiated Caco-2 cells that are incubated with AZA1 did not suffer noticeable viability alterations, in accordance with previous data [32]. Nevertheless, when assays were performed with immature cells, cytotoxicity was evident which lysosomes may be responsible [33]. …”

Section: Discussionsupporting

confidence: 77%

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Abal¹,

Louzao²,

Fraga-Corral³

et al. 2017

Cell Physiol Biochem

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Background: Azaspiracids (AZAs) are marine biotoxins produced by the dinoflagellates genera Azadinium and Amphidoma. These toxins cause azaspiracid poisoning (AZP), characterized by severe gastrointestinal illness in humans after the consumption of bivalve molluscs contaminated with AZAs. The main aim of the present study was to examine the consequences of human exposure to AZA1 by the study of absorption and effects of the toxin on Caco-2 cells, a reliable model of the human intestine. Methods: The ability of AZA1 to cross the human intestinal epithelium has been evaluated by the Caco-2 transepithelial permeability assay. The toxin has been detected and quantified using a microsphere-based immunoassay. Cell alterations and ultrastructural effects has been observed with confocal and transmission electron microscopy Results: AZA1 was absorbed by Caco-2 cells in a dose-dependent way without affecting cell viability. However, modifications on occludin distribution detected by confocal microscopy imaging indicated a possible monolayer integrity disruption. Nevertheless, transmission electron microscopy imaging revealed ultrastructural damages at the nucleus and mitochondria with autophagosomes in the cytoplasm, however, tight junctions and microvilli remained unaffected. Conclusion: After the ingestion of molluscs with the AZA1, the toxin will be transported through the human intestinal barrier to blood causing damage on epithelial cells.

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Section: Discussionsupporting

confidence: 77%

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Abal¹,

Louzao²,

Fraga-Corral³

et al. 2017

Cell Physiol Biochem

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“…The loss of lysosomal membrane integrity in haemocytes further suggests that these organelles are an early cellular target of AZAs. A key role of lysosomes in AZA-induced toxicity was proposed also by Ferron and colleagues in cultured cells exposed to AZA-1 [43], similarly to other purified biotoxins like yessotoxins [44], or toxic microalgae like Ostreopsis cf. ovata [45] and Alexandrium minutum [46].…”

Section: Discussionmentioning

confidence: 92%

“…Although the genotoxic effects of AZAs are poorly investigated, AZA-1, AZA-2 and AZA-3 did not induce DNA double-strand breaks in human cell lines [43]. Conversely, an increase of DNA fragmentation was observed in the haemocytes of mussels exposed to A. dexteroporum after 14 exposure days, even though such an increase was not significant at day 7 and 21.…”

Section: Discussionmentioning

confidence: 99%

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

et al. 2019

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Azaspiracids (AZAs) are marine biotoxins including a variety of analogues. Recently, novel AZAs produced by the Mediterranean dinoflagellate Azadinium dexteroporum were discovered (AZA-54, AZA-55, 3-epi-AZA-7, AZA-56, AZA-57 and AZA-58) and their biological effects have not been investigated yet. This study aimed to identify the biological responses (biomarkers) induced in mussels Mytilus galloprovincialis after the bioaccumulation of AZAs from A. dexteroporum. Organisms were fed with A. dexteroporum for 21 days and subsequently subjected to a recovery period (normal diet) of 21 days. Exposed organisms accumulated AZA-54, 3-epi-AZA-7 and AZA-55, predominantly in the digestive gland. Mussels’ haemocytes showed inhibition of phagocytosis activity, modulation of the composition of haemocytic subpopulation and damage to lysosomal membranes; the digestive tissue displayed thinned tubule walls, consumption of storage lipids and accumulation of lipofuscin. Slight genotoxic damage was also observed. No clear occurrence of oxidative stress and alteration of nervous activity was detected in AZA-accumulating mussels. Most of the altered parameters returned to control levels after the recovery phase. The toxic effects detected in M. galloprovincialis demonstrate a clear biological impact of the AZAs produced by A. dexteroporum, and could be used as early indicators of contamination associated with the ingestion of seafood.

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“…Ferron et al, 2016 [123], used the combination index-isobologram equation developed by Chou and Talalay [124] in order to deeply characterize the interactions between binary mixtures of phycotoxins incubated with human intestinal cells (Table 6). …”

Section: Toxicological Assessmentmentioning

confidence: 99%

Mixtures of Lipophilic Phycotoxins: Exposure Data and Toxicological Assessment

et al. 2018

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Lipophilic phycotoxins are secondary metabolites produced by phytoplanktonic species. They accumulate in filter-feeding shellfish and can cause human intoxication. Regulatory limits have been set for individual toxins, and the toxicological features are well characterized for some of them. However, phycotoxin contamination is often a co-exposure phenomenon, and toxicological data regarding mixtures effects are very scarce. Moreover, the type and occurrence of phycotoxins can greatly vary from one region to another. This review aims at summarizing the knowledge on (i) multi-toxin occurrence by a comprehensive literature review and (ii) the toxicological assessment of mixture effects. A total of 79 publications was selected for co-exposure evaluation, and 44 of them were suitable for toxin ratio calculations. The main toxin mixtures featured okadaic acid in combination with pectenotoxin-2 or yessotoxin. Only a few toxicity studies dealing with co-exposure were published. In vivo studies did not report particular mixture effects, whereas in vitro studies showed synergistic or antagonistic effects. Based on the combinations that are the most reported, further investigations on mixture effects must be carried out.

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Combined Effects of Lipophilic Phycotoxins (Okadaic Acid, Azapsiracid-1 and Yessotoxin) on Human Intestinal Cells Models

Cited by 22 publications

References 53 publications

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Absorption and Effect of Azaspiracid-1 Over the Human Intestinal Barrier

Biological Effects of the Azaspiracid-Producing Dinoflagellate Azadinium dexteroporum in Mytilus galloprovincialis from the Mediterranean Sea

Mixtures of Lipophilic Phycotoxins: Exposure Data and Toxicological Assessment

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