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EFFECTS OF SYNTHETIC CIGUATOXIN CTX3C AND GAMBIERONE IN NEURONAL CELLS

Andrea Boente-Juncal1, Carmen Vale1, Amparo Alfonso1, Masahiro Hirama2, Shuji Yamashita2, Mercedes Camiña3, Mercedes M. Vieytes3 and Luis M. Botana1*
  • 1 Departamento Farmacología,Farmacia y Tecnología Farmacéutica. Facultad Veterinaria Lugo, Universidad Santiago de Compostela, Spain
  • 2 Department of Chemistry, Graduate School of Science, Tohoku University, Japan
  • 3 Departamento de Fisiología, Facultad Veterinaria, Universidad de Santiago de Compostela, Spain

Ciguatera food poisoning (CFP) is one of the most widespread and fearful form of seafood poisoning, is caused by the consumption of fish containing ciguatoxins (CTXs) produced by microalgae of the genus Gambierdiscus (Bagnis et al., 1979) and Fukuyoa (Gomez et al., 2015). It is the most common non-bacterial seafood-related illness and it is characterized by a variety of gastrointestinal and neurological symptoms, and on rare occasions, death (Friedman et al., 2017).The global incidence rates of CFP range from 50,000 to 500,000 annually, although under-diagnosis and under-reporting occur. It is estimated that only about 8–20% of CFP cases are reported to the relevant health authorities due to a number of challenges such as the lack of fast and cost-effective CTX detection methods and non-specific nature of CFP symptoms leading to misdiagnosis. Marine dinoflagellate of the genus Gambierdiscus produce several bioactive polyether compounds such as maitotoxins (MTXs), ciguatoxins, gambierol (Watters, 1995; Lewis, 2001; Pearn, 2001; Yasumoto, 2001) and the recently identified ladder-shapped polyether gambierone (Rodriguez et al., 2015). The most common symptoms of ciguatera, comprise gastrointestinal and cardiac disturbances as well as neurological alterations, such as intense pruritus, painful dysesthesias, allodynia, ataxia, and hyperalgesia, among others (Friedman et al., 2017). The synthetic ciguatoxin CTX 3C is a highly lipophilic cyclic polyether compound characterized by 13 ether rings (Yasumoto, 2001) while the structure of gambierone comprises a polyether skeleton with a right-hand side chain (Rodriguez et al., 2015). Although the chemical structure of ciguatoxin and gambierone are different, both compounds have a similar molecular weight and preliminary studies showed that they had a similar biological activity causing activation of voltage-dependent sodium channels at hyperpolarizing potentials, however gambierone showed a lower potency than CTX3C (Rodriguez et al., 2015). In this work the effects of both CTX3C and gambierone on glutamate neurotransmission were evaluated in human neuronal stem cells and in primary cultures of cerebellar granule cells. None of the compounds affected human neuronal stem cell viability but chronic exposure of human neuronal stem cells to these compounds modified glutamate receptor expression. Moreover, in primary cultures of cerebellar granule cells treated during 48 hours with CTX3C or gambierone, both compounds decreased the cytosolic calcium increase evoked by bath application of glutamate. All together these results confirm that gambierone has a biological activity similar to CTX3C.

Acknowledgements

The research has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD and ITC-20161072. From European Union POCTEP 0161-Nanoeaters-1-E-1, and Interreg AlertoxNet EAPA-317-2016. ABJ is recipient a fellowship from the Spanish Ministry Education.

References

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Keywords: Ciguatera food poisoning, CTX3C, Gambierone, cerebellar granule cells, human neuronal stem cells

Conference: IMMR'18 | International Meeting on Marine Research 2018, Peniche, Portugal, 5 Jul - 6 Jul, 2018.

Presentation Type: Poster Presentation

Topic: Blue Biotech

Citation: Boente-Juncal A, Vale C, Alfonso A, Hirama M, Yamashita S, Camiña M, Vieytes MM and Botana LM (2019). EFFECTS OF SYNTHETIC CIGUATOXIN CTX3C AND GAMBIERONE IN NEURONAL CELLS. Front. Mar. Sci. Conference Abstract: IMMR'18 | International Meeting on Marine Research 2018. doi: 10.3389/conf.FMARS.2018.06.00023

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Received: 28 Apr 2018; Published Online: 07 Jan 2019.

* Correspondence: Prof. Luis M Botana, Departamento Farmacología,Farmacia y Tecnología Farmacéutica. Facultad Veterinaria Lugo, Universidad Santiago de Compostela, Lugo, 27002, Spain, luis.botana@usc.es