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Marine and Freshwater Toxins pp 193–217Cite as

Spirolides and Cyclic Imines: Toxicological Profile

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Part of the book series: Toxinology ((TOXI))

Abstract

In this chapter, available evidence on the toxicological profile of spirolides and other lipophilic cyclic imine toxins is reviewed, highlighting their chemical structure, the phytoplankton species involved in their production, their pharmacokinetics/toxicokinetics and experimental toxicity, and their molecular targets and mechanisms of action. These phycotoxins belong to an emerging class of chemical agents associated with marine algal blooms and shellfish toxicity. Their chemical structure is represented by a macrocycle, with the ring size between 14 and 27, and two conserved features that include the cyclic imine group and spiroketal ring system. The producers of spirolides, gymnodimines, and pinnatoxins have been identified as being the dinoflagellates Alexandrium ostenfeldii/peruvianum, Karenia selliformis, and Vulcanodinium rugosum. Their acute toxicity, appraised by the mouse bioassays, classifies them as “fast-acting” toxins because they induce rapid onset of neurological symptoms followed by death within a few minutes. The spirolide congeners are the most toxic after intraperitoneal injection, while there are indications that pinnatoxins are the most toxic group after oral administration. The neurotoxic effects reported for these phycotoxins are mostly due to their specific interaction with the muscle and neuronal types of nicotinic acetylcholine receptors which are the principal molecular targets of spirolides, gymnodimines, and pinnatoxins, so far studied. Hence, these phycotoxins exhibit both high affinity and broad specificity on nicotinic receptors, indicating that their sites of interaction in the receptors include amino acid residues highly conserved among animal species.

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Acknowledgments

Work performed in the laboratory of authors was funded by the “Agence Nationale de la Recherche” (France, grant AQUANEUROTOX ANR-12-ASTR-0037-1) and by the National Institutes of Health (USA, grant NIGMS R01 GM077379 to A.Z).

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Authors and Affiliations

  1. Institut des Neurosciences Paris–Saclay, UMR 9197 CNRS/Université Paris–Sud, 91190, Gif–sur–Yvette, France

    Jordi Molgó, Evelyne Benoit & Rómulo Aráoz

  2. Service d’Ingénierie Moléculaire des Protéines, Laboratoire de Toxinologie Moléculaire et Biotechnologies, CEA, Institut de Biologie et Technologies de Saclay, Building 152, letter No. 24, 91191, Gif–sur–Yvette, France

    Jordi Molgó, Evelyne Benoit & Rómulo Aráoz

  3. Department of Chemistry and Biochemistry, University of California, Santa Barbara, CA, 93106, USA

    Armen Zakarian

  4. CNRS, Institut de Chimie des Substances Naturelles, UPR 2301, Labex LERMIT, 91198, Gif–sur–Yvette, France

    Bogdan I. Iorga

Authors
  1. Jordi Molgó
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  2. Evelyne Benoit
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  3. Rómulo Aráoz
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  4. Armen Zakarian
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  5. Bogdan I. Iorga
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Corresponding authors

Correspondence to Jordi Molgó or Bogdan I. Iorga .

Editor information

Editors and Affiliations

  1. Dept of Anatomy, Natl Univ of Singapore, Singapore, Singapore

    P. Gopalakrishnakone

  2. Universidade Estadual Paulista, Botucatu, São Paulo, Brazil

    Vidal Haddad Jr.

  3. Department of Life Sciences, University of Trieste, Trieste, Italy

    Aurelia Tubaro

  4. College of Veterinary Medicine, Gyeongsang National University, Jinju, Korea (Republic of)

    Euikyung Kim

  5. College of Medicine, University of Florida, Gainesville, Florida, USA

    William R. Kem

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Molgó, J., Benoit, E., Aráoz, R., Zakarian, A., Iorga, B.I. (2016). Spirolides and Cyclic Imines: Toxicological Profile. In: Gopalakrishnakone, P., Haddad Jr., V., Tubaro, A., Kim, E., Kem, W. (eds) Marine and Freshwater Toxins. Toxinology. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-6419-4_23

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