The marine biotoxin okadaic acid affects intestinal tight junction proteins in human intestinal cells

Dietrich, Jessica; Grass, Irina; Günzel, Dorothee; Herek, Saadet; Braeuning, Albert; Lampen, Alfonso; Hessel-Pras, Stefanie

doi:10.1016/j.tiv.2019.03.033

Cited by 22 publications

(10 citation statements)

References 77 publications

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“…Due to the human health concerns associated with DSP, OA group of phycotoxins are tightly regulated by European Union legislation (Union 2011 ). Even though many in vitro and in vivo studies have been performed with OA, there are still many gaps about the targets involved in its acute oral toxicity (Louzao et al 2021 ; Huguet et al 2020 ; Dietrich et al 2019 ; Reale et al 2019 ; Tripuraneni et al 1997 ; Ferron et al 2014 ; Vilarino et al 2018 ). It is stated in the literature that okadaic acid group of toxins are inhibitors of Ser/Thr protein phosphatases 1 (PP1) and 2A (PP2A) which play many roles in the cell (Takai et al 1992 ).…”

Section: Discussionmentioning

confidence: 99%

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

et al. 2021

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The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3–36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3–36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.

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Section: Discussionmentioning

confidence: 99%

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

et al. 2021

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“…Many different compounds belong to the last group, such as okadaic acid (OA) and its analogues dinophysistoxins (DTX1, DTX2 and DTX3), that are the most common in the European countries (Alves et al 2019) and together with azaspiracids (AZA1, AZA2 and AZA3) cause the diarrhetic shell sh poisoning (DSP) outbreaks, while pectenotoxins (PTXs) and yessotoxins (YTXs) are not proven to provoke such symptoms after their ingestion (Hassoun et al 2021). The main symptoms of OA intoxication are nausea, vomiting, abdominal pain and diarrhea appearing within 30 min up to few hours and declining generally after 3 days (Dietrich et al 2019). The toxicity of DTX1 is very similar to OA, whereas DTX2 and DTX3 are less toxic (Sitprija and Sitprija 2019).…”

Section: Introductionmentioning

confidence: 99%

Surveillance Plan of Lipophilic Marine Biotoxins in Molluscs from the Croatian Coast

et al. 2021

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In the present study, a 4-year surveillance plan for the detection of lipophilic marine biotoxins in Mytilus galloprovincialis and Callista chione from different aquaculture farms and natural beds along the Central Adriatic coasts of Croatia was reported. The samples were analyzed by a validated LC-MS/MS method in accordance with the Regulation (EU) No 2019/627. Lipophilic marine biotoxins belonging to the okadaic acid group, except for azaspiracids, as well as yessotoxins were found at different concentrations, always below the maximum limits established by the Regulation (EC) No 853/2004. The seasonal distribution showed the highest values in summer months, and an interannual variability was also observed, probably due to environmental conditions aging on the density of harmful algal blooms. The comprehensive data reported in this study should help the future research in making advancing prediction models along the Eastern Adriatic coast.

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“…1.6.1.1 Okadaic acid Okadaic acid (OA) is a lipophilic phycotoxin (Figure 1.2) found in shellfish and causes diarrheic shellfish poisoning (DSP) upon human consumption of contaminated tissue and is produced by dinoflagellates of the genera Dinophysis and Prorocentrum (Dietrich et al, 2019).…”

Section: Gut Specific Challenges 161 Marine Biotoxinsmentioning

confidence: 99%

“…TJ and AJ are regulated through protein phosphatases 1 and 2A (PP1 and PP2A) and protein kinases in rats and humans. The exact mode of OA's increased permeability remains unclear, it has been suggested to involve inhibiting PPA2 and PP1 (Bialojan and Takai, 1988) or through disrupting F-actin cytoskeleton with is involved in TJ control (Fiorentini et al, 1996, Dietrich et al, 2019.…”

Section: Gut Specific Challenges 161 Marine Biotoxinsmentioning

confidence: 99%

“…The general structure of okadaic acid (Dietrich et al, 2019) 1.6.1.2 Azaspiracids Azaspiracids (AZAs) are also lipophilic polyether toxinsfirst detected in 1995 from a contaminated batch of mussels on the West coast of Ireland. AZAs represent one of the most potent marine toxins, which induce similar gastrointestinal distress as observed in OA (Román et al, 2002).…”

Section: Figure 12mentioning

confidence: 99%

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Prospecting the insect model, Galleria mellonella, for gut-related pathobiology

Emery¹

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Animal research has contributed immensely to medical and scientific advances over the last century, and continues to play important roles in enhancing our understanding of infectious and non-communicable disease development, and the search for treatments. The mouse, for example, shares ~95% of human genes and is the most widespread vertebrate model in use. Since the late 1980s, there has been several UK and EU directives (e.g., 2010/63/EU) to improve the welfare of animals considered essential for experimentation, and to link directly with the principle of the 3Rs, to Replace, Reduce and Refine animal use. Additionally, animal maintenance, husbandry, compliance with legislation and licencing, and staff training are costly and time-consuming. Hence, there is much to gain from developing alternative in vivo models and complementary in vitro, in chemico and in silico tools. Larvae of the wax moth Galleria mellonella represent one such surrogate to rodents, and have been used successfully to study microbial isolates for virulence traits, putative antibiotic therapies, and more recently, toxicological assessment. There is an abundance of practical and biological advantages to selecting G. mellonella over rodents and traditional non-mammalian fruit flies and nematodes (which are described in Chapter 1), but one area lacking in knowledge is their applicability for studies of gut pathobiology. Therefore, the aim of this thesis was to evaluate the usefulness and accuracy of G. mellonella larvae as a model for gut specific toxins and pathogens when administered through an oral route (gavage). A series of whole-organism (phenotype), cellular, biochemical, microbiological and microscopy methods were used to interrogate the gastrointestinal tract of G. mellonella in the absence and presence of chemicals and microbes known to cause gastropathy in rodents and humans. First, the transferability of the indomethacin restraint/ulcer assay was established in G. mellonella, with levels of tissue deterioration and enhanced leakiness reminiscent of rodents (Chapter 2). Second, the rearing of insects on nutraceuticals Cordyceps sinensis and bovine colostrum alleviated gut damage caused by indomethacin, and improved survival outcomes when challenged with the enteric pathogen Campylobacter jejuni (Chapter 3). Third, oral administration of shellfish poisoning toxins (okadaic acid and azaspiracids 1-3) to G. mellonella, interfered with tissue integrity and microbial stability of the gastrointestinal tract, and produced comparable LD50 levels to their rodent counterparts (Chapter 4). The results presented here go beyond establishing synonymous damage phenomena between G. mellonella larvae and vertebrates (Chapter 5), but adds new knowledge to the structure and function of the lepidopteran alimentary canal, the cytopathology of emerging marine toxins, and how diet invariably influences a host’s capacity to recover from subacute chemical and microbial disruptors.

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The marine biotoxin okadaic acid affects intestinal tight junction proteins in human intestinal cells

Cited by 22 publications

References 77 publications

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

Serotonin involvement in okadaic acid-induced diarrhoea in vivo

Surveillance Plan of Lipophilic Marine Biotoxins in Molluscs from the Croatian Coast

Prospecting the insect model, Galleria mellonella, for gut-related pathobiology

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