1. Cyclic imine toxins survey in coastal european shellfish samples: Bioaccumulation and mode of action of 28-O-palmitoyl ester of pinnatoxin-G. first report of portimine-A bioaccumulation.
- Author
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Aráoz, Rómulo, Barnes, Paul, Séchet, Véronique, Delepierre, Muriel, Zinn-Justin, Sophie, Molgó, Jordi, Zakarian, Armen, Hess, Philipp, and Servent, Denis
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SHELLFISH , *CHOLINERGIC receptors , *BINDING site assay , *MARINE toxins , *NICOTINIC acetylcholine receptors , *BIOACCUMULATION , *TOXINS , *ESTERS - Abstract
• The non-regulated cyclic imine toxins are potent antagonists of muscle/neuronal nAChRs. • Robust bioassay for fast & early detection of cyclic imine toxins in shellfish samples. • High incidence of cyclic imine toxins in shellfish collected in eight european countries. • First report showing the bioaccumulation of the apoptosis-inducer portimine in mussels. • We determined the mode of action of 28- O -palmitoyl ester of pinnatoxin-G on nAChR. Cyclic imine toxins exhibit fast acting neurotoxicity and lethality by respiratory arrest in mice explained by their potent antagonistic activity against muscular nicotinic acetylcholine receptors. We performed a survey of gymnodimine-A, 13-desmethyl spirolide-C, 13,19-didesmethyl spirolide-C, 20-methyl spirolide-G, pinnatoxin-A, pinnatoxin-G, portimine-A and 28- O -palmitoyl ester of pinnatoxin-G in 36 shellfish samples collected in coastal areas of 8 European countries using a microplate receptor binding assay and UPLC-MS/MS for toxin identification and quantification. The major toxins found in these samples were pinnatoxin-G, 20-methyl spirolide-G, 13-desmethyl spirolide-C, gymnodimine-A and portimine-A. Traces of 13,19-didesmethyl spirolide-C, pinnatoxin-A and 28- O -palmitoyl ester of pinnatoxin-G were also detected. The rapid death of mice was correlated with higher pinnatoxin-G concentrations in mussel digestive gland extracts injected intraperitoneally. Our survey included nontoxic control samples that were found to contain moderate to trace amounts of several cyclic imine toxins. Shellfish may bioaccumulate not only cyclic imine toxins but also a large number of acyl derivatives as a product of metabolic transformation of these neurotoxins. This is the first report in which portimine-A and 28- O -palmitoyl ester of pinnatoxin-G were detected in shellfish extracts from digestive glands of mussels collected in Ingril lagoon. The bioaccumulation of portimine-A is particularly of concern because it is cytotoxic and is able to induce apotosis. The mode of action of 28- O -palmitoyl ester of pinnatoxin-G was studied by receptor binding-assay and by two-electrode voltage clamp electrophysiology. The antagonistic behavior of the acylated pinnatoxin-G towards nicotinic acetylcholine receptor of muscle type is shown here for the first time. Since cyclic imine toxins are not regulated further monitoring of these emerging toxins is needed to improve evidence gathering of their occurrence in shellfish commercialized for human consumption in Europe given their potent antagonism against muscle and neuronal nicotinic acetylcholine receptors. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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