Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4

Martín-López, Alicia; Gallardo, Juan José; Sánchez-Mirón, A.; Camacho, F. Garcı́a; Grima, E. Molina

doi:10.1016/j.toxicon.2012.07.008

Cited by 27 publications

(16 citation statements)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another possible explanation for TEER reduction could be the disruption of the actin cytoskeleton by DTX1, since the cytoskeleton is important for mechanical stability and the integrity of epithelial cells and tissues. This effect was already reported in several in vitro cell cultures treated with OA [29,42,43,44,45]. Some of the main domains of the plasma membrane, where actin filaments are concentrated, are substrate adhesion sites [46].…”

Section: Discussionsupporting

confidence: 54%

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

Fernández

Louzao

Fraga-Corral

et al. 2014

Toxins

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionsupporting

confidence: 54%

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

Fernández

Louzao

Fraga-Corral

et al. 2014

Toxins

View full text Add to dashboard Cite

show abstract

“…In this study, OA induced an important stimulation of IL-8 production at both transcriptional and post-transcriptional levels. A recent in vitro study employing mouse T lymphocytes also reported that low concentrations of OA (5 nM), within the range previously detected in mice bloodstream after oral administration, induced down-regulation of T cell receptor (TCR) expression levels in these cells, compromising the T cell activation and, consequently, the immune response [108]. …”

Section: Oa Beyond Its Role As Dsp Inductormentioning

confidence: 87%

Okadaic Acid: More than a Diarrheic Toxin

et al. 2013

View full text Add to dashboard Cite

Okadaic acid (OA) is one of the most frequent and worldwide distributed marine toxins. It is easily accumulated by shellfish, mainly bivalve mollusks and fish, and, subsequently, can be consumed by humans causing alimentary intoxications. OA is the main representative diarrheic shellfish poisoning (DSP) toxin and its ingestion induces gastrointestinal symptoms, although it is not considered lethal. At the molecular level, OA is a specific inhibitor of several types of serine/threonine protein phosphatases and a tumor promoter in animal carcinogenesis experiments. In the last few decades, the potential toxic effects of OA, beyond its role as a DSP toxin, have been investigated in a number of studies. Alterations in DNA and cellular components, as well as effects on immune and nervous system, and even on embryonic development, have been increasingly reported. In this manuscript, results from all these studies are compiled and reviewed to clarify the role of this toxin not only as a DSP inductor but also as cause of alterations at the cellular and molecular levels, and to highlight the relevance of biomonitoring its effects on human health. Despite further investigations are required to elucidate OA mechanisms of action, toxicokinetics, and harmful effects, there are enough evidences illustrating its toxicity, not related to DSP induction, and, consequently, supporting a revision of the current regulation on OA levels in food.

show abstract

“…Disruption of the F-actin cytoskeleton by OA has been observed in several cell types in vitro [58,74,88,89], and it was suggested that such a change could decrease the patency of TJs [74] and, thus, lead to diarrhoea in vivo . It has been shown, however, that methyl okadaate, which has little or no effect on the activities of PP2A and PP1, was of similar activity to OA in disrupting the F-actin cytoskeleton in hepatocytes [58] and in neuroblastoma cells [90].…”

Section: Involvement Of Protein Phosphatase Inhibition In the Toximentioning

confidence: 99%

“…OA induces TNFα release from cells in vitro [95], and this cytokine has been shown to increase paracellular permeability in cultured epithelial monolayers [96]. OA has also been shown to generate highly oxidising active oxygen species in cells in vitro [89,97,98], and oxidative stress is known to increase paracellular permeability [86,99]. Hosokawa et al [75] demonstrated increased paracellular permeability in the rat colon in vivo , which was associated with the formation of micro-thrombi in the submucosal venules, followed by mucosal oedema.…”

Section: Involvement Of Protein Phosphatase Inhibition In the Toximentioning

confidence: 99%

Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?

Munday

2013

Toxins

View full text Add to dashboard Cite

Okadaic acid (OA) and its derivatives, which are produced by dinoflagellates of the genera Prorocentrum and Dinophysis, are responsible for diarrhetic shellfish poisoning in humans. In laboratory animals, these toxins cause epithelial damage and fluid accumulation in the gastrointestinal tract, and at high doses, they cause death. These substances have also been shown to be tumour promoters, and when injected into the brains of rodents, OA induces neuronal damage reminiscent of that seen in Alzheimer’s disease. OA and certain of its derivatives are potent inhibitors of protein phosphatases, which play many roles in cellular metabolism. In 1990, it was suggested that inhibition of these enzymes was responsible for the diarrhetic effect of these toxins. It is now repeatedly stated in the literature that protein phosphatase inhibition is not only responsible for the intestinal effects of OA and derivatives, but also for their acute toxic effects, their tumour promoting activity and their neuronal toxicity. In the present review, the evidence for the involvement of protein phosphatase inhibition in the induction of the toxic effects of OA and its derivatives is examined, with the conclusion that the mechanism of toxicity of these substances requires re-evaluation.

show abstract

Cytotoxicity of yessotoxin and okadaic acid in mouse T lymphocyte cell line EL-4

Cited by 27 publications

References 33 publications

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

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

Okadaic Acid: More than a Diarrheic Toxin

Is Protein Phosphatase Inhibition Responsible for the Toxic Effects of Okadaic Acid in Animals?

Contact Info

Product

Resources

About