Analysis of the action of gymnodimine-A and 13-desmethyl spirolide C on the mouse neuromuscular system in vivo

Marrouchi, Riadh; Rome, Guillaume; Kharrat, Riadh; Molgó, Jordi; Benoit, Évelyne

doi:10.1016/j.toxicon.2013.08.050

Cited by 22 publications

(16 citation statements)

References 26 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…) and 6 ng/kg for 13‐desmethyl spirolide C, which in turn was about 300‐fold more active than gymnodimine A on an equimolar basis (Marrouchi et al . ). Overall, these studies indicated that these cyclic imine toxins potently block neuromuscular transmission on junctions expressing the mature muscle‐type (α1 2 β1δε) nAChR.…”

Section: Mode Of Action On Muscle‐type Nachrsmentioning

confidence: 97%

Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors

Molgó

Marchot

Aráoz

et al. 2017

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

We present an overview of the toxicological profile of the fast acting, lipophilic macrocyclic imine toxins, an emerging family of organic compounds associated with algal blooms, shellfish contamination and neurotoxicity. Worldwide, shellfish contamination incidents are expanding; therefore the significance of these toxins for the shellfish food industry deserves further study. Emphasis is directed to the dinoflagellate species involved in their production, their chemical structures, and their specific mode of interaction with their principal natural molecular targets, the nicotinic acetylcholine receptors, or with the soluble acetylcholine-binding protein, used as a surrogate receptor model. The dinoflagellates Karenia selliformis and Alexandrium ostenfeldii / A. peruvianum have been implicated in the biosynthesis of gymnodimines and spirolides, while Vulcanodinium rugosum is the producer of pinnatoxins and portimine. The cyclic imine toxins are characterized by a macrocyclic skeleton comprising 14 to 27 carbon atoms, flanked by two conserved moieties, the cyclic imine and the spiroketal ring system. These phycotoxins generally display high affinity and broad specificity for the muscle-type and neuronal nicotinic acetylcholine receptors, a feature consistent with their binding site at the receptor subunit interfaces, composed of residues highly conserved among all nAChRs, and explaining the diverse toxicity among animal species.

show abstract

Section: Mode Of Action On Muscle‐type Nachrsmentioning

confidence: 97%

Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors

Molgó

Marchot

Aráoz

et al. 2017

Journal of Neurochemistry

Self Cite

View full text Add to dashboard Cite

show abstract

“…The toxicological information for CIs is limited, comprising mostly acute toxicity studies [1]. In addition, not all CIs are equally potent: SPX-1 showed about 300 fold more activity than GYM-A on equimolar basis in an in vivo study about neuromuscular excitability in mice [7]. Oral toxicity of SPXs is much lower (10-100 times less toxic orally, depending on the toxin and how the toxins are administered).…”

Section: Introductionmentioning

confidence: 99%

Occurrence of cyclic imines in European commercial seafood and consumers risk assessment

Rambla-Alegre

Miles

Iglesia

et al. 2018

Environmental Research

View full text Add to dashboard Cite

Cyclic imines constitute a quite recently discovered group of marine biotoxins that act on neural receptors and that bioaccumulate in seafood. They are grouped together due to the imino group functioning as their common pharmacore, responsible for acute neurotoxicity in mice. Cyclic imines (CIs) have not been linked yet to human poisoning and are not regulated in the European Union (EU), although the European Food Safety Authority (EFSA) requires more data to perform conclusive risk assessment for consumers. Several commercial samples of bivalves including raw and processed samples from eight countries (Italy, Portugal, Slovenia, Spain, Ireland, Norway, The Netherlands and Denmark) were obtained over 2 years. Emerging cyclic imine concentrations in all the samples were analysed on a LC-3200QTRAP and LC-HRMS QExactive mass spectrometer. In shellfish, two CIs, pinnatoxin G (PnTX-G) and 13-desmethylspirolide C (SPX-1) were found at low concentrations (0.1-12µg/kg PnTX-G and 26-66µg/kg SPX-1), while gymnodimines and pteriatoxins were not detected in commercial (raw and processed) samples. In summary, SPX-1 (n: 47) and PnTX-G (n: 96) were detected in 9.4% and 4.2% of the samples, respectively, at concentrations higher than the limit of quantification (LOQ), and in 7.3% and 31.2% of the samples at concentrations lower than the LOQ (25µg/kg for SPX-1 and 3µg/kg for PnTX-G), respectively. For the detected cyclic imines, the average exposure and the 95th percentile were calculated. The results obtained indicate that it is unlikely that a potential health risk exists through the seafood diet for CIs in the EU. However, further information about CIs is necessary in order to perform a conclusive risk assessment.

show abstract

“…The mechanism of action is the same for all studied cyclic imines [1,2,21] and both GYM-A and SPX-1 show high affinity and slow dissociation of the bound ligand to their receptors [22,23]. Nevertheless, not all cyclic imines are equally potent: SPX-1 showed about 300 fold more activity than GYM-A on equimolar basis in a in vivo study about neuromuscular excitability in mice [24]. To date, there is still a lack of information on the chronic toxicity of cyclic imines.…”

Section: Introductionmentioning

confidence: 99%

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

et al. 2014

View full text Add to dashboard Cite

Cyclic imines are lipophilic marine toxins that bioaccumulate in seafood. Their structure comprises a cyclic-imino moiety, responsible for acute neurotoxicity in mice. Cyclic imines have not been linked yet to human poisonings and are not regulated in Europe, although the European Food Safety Authority requires more data to perform a conclusive risk assessment for consumers. This work presents the first detection of pinnatoxin G (PnTX-G) in Spain and 13-desmethyl spirolide C (SPX-1) in shellfish from Catalonia (Spain, NW Mediterranean Sea). Cyclic imines were found at low concentrations (2 to 60 µg/kg) in 13 samples of mussels and oysters (22 samples analyzed). Pinnatoxin G has been also detected in 17 seawater samples (out of 34) using solid phase adsorption toxin tracking devices (0.3 to 0.9 µg/kg-resin). Pinnatoxin G and SPX-1 were confirmed with both low and high resolution (<2 ppm) mass spectrometry by comparison of the response with that from reference standards. For other analogs without reference standards, we applied a strategy combining low resolution MS with a triple quadrupole mass analyzer for a fast and reliable screening, and high resolution MS LTQ Orbitrap® for unambiguous confirmation. The advantages and limitations of using high resolution MS without reference standards were discussed.

show abstract

Analysis of the action of gymnodimine-A and 13-desmethyl spirolide C on the mouse neuromuscular system in vivo

Cited by 22 publications

References 26 publications

Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors

Cyclic imine toxins from dinoflagellates: a growing family of potent antagonists of the nicotinic acetylcholine receptors

Occurrence of cyclic imines in European commercial seafood and consumers risk assessment

Confirmation of Pinnatoxins and Spirolides in Shellfish and Passive Samplers from Catalonia (Spain) by Liquid Chromatography Coupled with Triple Quadrupole and High-Resolution Hybrid Tandem Mass Spectrometry

Contact Info

Product

Resources

About