Sublethal doses of dinophysistoxin-1 and okadaic acid stimulate secretion of inflammatory factors on innate immune cells: Negative health consequences

Campo, Miguel del; Zhong, Ta-Ying; Tampe, Ricardo; Garcı́a, Lorena; Lagos, Néstor

doi:10.1016/j.toxicon.2016.12.005

Cited by 14 publications

(8 citation statements)

References 35 publications

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“…One proposed mechanism to explain the role of DSP toxins as tumor promoters involves an increase in the synthesis and secretion of TNF-α [ 161 ]. It was recently demonstrated that OA and DTX1 at sublethal doses stimulate secretion of inflammatory factors [ 162 ]. Furthermore, sublethal doses of OA can increase cellular mitosis in vivo and activate events involved in the inflammatory response and carcinogenesis [ 163 ].…”

Section: Okadaic Acid Groupmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

123

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Marine biotoxins are produced by aquatic microorganisms and accumulate in shellfish or finfish following the food web. These toxins usually reach human consumers by ingestion of contaminated seafood, although other exposure routes like inhalation or contact have also been reported and may cause serious illness. This review shows the current data regarding the symptoms of acute intoxication for several toxin classes, including paralytic toxins, amnesic toxins, ciguatoxins, brevetoxins, tetrodotoxins, diarrheic toxins, azaspiracids and palytoxins. The information available about chronic toxicity and relative potency of different analogs within a toxin class are also reported. The gaps of toxicological knowledge that should be studied to improve human health protection are discussed. In general, gathering of epidemiological data in humans, chronic toxicity studies and exploring relative potency by oral administration are critical to minimize human health risks related to these toxin classes in the near future.

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Section: Okadaic Acid Groupmentioning

confidence: 99%

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Vilariño

Louzao

Abal

et al. 2018

Toxins

123

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“…In recent years, DTX-1 was found to be more toxic, 14 especially with respect to oral toxicity. 15 DTX-1 can destroy the integrity of epithelial cells, and play an important role in apoptosis, 16 which induces the same cytotoxic effects with 1/5 concentrations of OA. 17 While the effect of DTX-1 on pro-inammatory and carcinogenicity of macrophages is ten times more than that of OA.…”

Section: Introductionmentioning

confidence: 99%

“…17 While the effect of DTX-1 on pro-inammatory and carcinogenicity of macrophages is ten times more than that of OA. 16 Studies have shown that the deposition rate of DTX-1 in the shellsh digestive gland is higher than that of OA. 18 However, DTX-1 cannot be detected effectively.…”

Section: Introductionmentioning

confidence: 99%

Selection and application of aptamers with high-affinity and high-specificity against dinophysistoxin-1

Zhou

et al. 2020

RSC Adv.

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“…Humans are intoxicated with DSP toxins by eating shellfish contaminated with these phycotoxins, which accumulate these in the midgut gland after filter feeding on DSP toxin producing microalgae [8]. A safe limit of 160 μg OA equivalents/kg shellfish meat has been established by the Food and Agriculture Organization [9], but during recent years studies have reported that OA concentrations below this safe limit stimulate the secretion of inflammatory factors by innate immune cells [10], which are linked to chronic inflammatory processes and cancer [11]. PP2A has a higher affinity for MC-LR than for OA and MC-LR thus is the stronger PP2A inhibitor (2to 10-fold more than OA) [12].…”

Section: Introductionmentioning

confidence: 99%

“…PP2A has a higher affinity for MC-LR than for OA and MC-LR thus is the stronger PP2A inhibitor (2to 10-fold more than OA) [12]. This remarkable observation is the reason that the authors proposed zero tolerance to DSP toxins in shellfish for human consumption [11]. Hence it is imperative to have a highly sensitive tool in order to monitor and quantify these phycotoxins to prevent contact with and deleterious effects on the human population [13,14].…”

Section: Introductionmentioning

confidence: 99%

High Yield Purification of Mytilidae PP2A: An Enzyme for the Sensitive Detection of Phycotoxins

Sepúlveda¹

2019

IJBP

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Diarrheic Shellfish Poison (DSP) toxins such as Okadaic Acid (OA), Dinophisis toxin 1 and Dinophisis toxin 2, and Microcystins such as Microcystin-LR (MC-LR) are widely spread biotoxins whose molecular mechanism of action is based on the specific inhibition of protein phosphatase 2A (PP2A) with costly negative effects on public health, even at lower quantities than those established by international safe limits worldwide, due to their tumor-promoting action and hepatotoxicity. Considering these, a zero tolerance on the human consumption of these phycotoxins should be advocated. The high affinity of these phycotoxins for PP2A allows using the same enzyme as a very sensitive biosensor. Until now, PP2A has been purified following the classic protocol to produce this enzyme that is based on mammalian tissue as the source material. However, it is characterized by its low PP2A content, resulting in low yields per gram of tissue. In this study PP2A was purified from an invertebrate, a native Chilean shellfish classified as Aulacomia atra. This Mytilidae is a common endemic shellfish that evolved together with the dinoflagellate DSP phycotoxin producers in the Chilean littoral. When the tissue of these shellfish is tested for PP2A, the data show an unusually high amount of this enzyme per gram of shellfish, using these shellfish, the yield post-purification was forty times greater than those reported for other mammalian PP2A purifications. This Mytilidae PP2A is characterized by a Vmax of 7.60 pmol min-1 μg protein-1 and a Km of 32.09 mM for p-NPP. The inhibition assay resulted in an IC50 for OA and MC-LR of 0.86 ng mL-1 and 0.437 ng mL-1 , respectively. The enzymatic stability over time was evaluated, showing that the enzyme is best kept at 4°C suspended in 10% of glycerol and as such retained 80% of its enzymatic activity after 2 weeks and 60% after more than 4 weeks. Taken together, these results indicate that PP2A purified from this bivalve filter-feeder mollusk is a good candidate biosensor for the detection and

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Sublethal doses of dinophysistoxin-1 and okadaic acid stimulate secretion of inflammatory factors on innate immune cells: Negative health consequences

Cited by 14 publications

References 35 publications

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Human Poisoning from Marine Toxins: Unknowns for Optimal Consumer Protection

Selection and application of aptamers with high-affinity and high-specificity against dinophysistoxin-1

High Yield Purification of Mytilidae PP2A: An Enzyme for the Sensitive Detection of Phycotoxins

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