Pharmacology of ciguatoxins

Vale, Carmen; Antelo, Álvaro; Martı́n, Victor S.

doi:10.1002/9781118500354.ch2

Cited by 4 publications

(4 citation statements)

References 93 publications

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“…Up to now, four toxin analogs designated as maitotoxin-1 (MTX1), maitotoxin-2 (MTX2), maitotoxin-3 (MTX3) and maitotoxin-4 (MTX4) isolated from different strains of these dinoflagellates have been identified in this toxin group [ 1 , 10 , 12 , 13 ]. So far, maitotoxin (MTX1) is the largest non-polymeric carbon chain molecule in nature [ 14 , 15 ]. Additionally, species of Gambierdiscus and Fukuyoa have been shown to produce other non-structurally related polyether analogs such as gambieric acids [ 16 ], gambieroxide [ 17 ], gambierol [ 18 ], and the recently identified gambierone [ 19 ].…”

Section: Introductionmentioning

confidence: 99%

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus

Boente-Juncal

Alvarez²,

Antelo³

et al. 2019

Toxins

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Gambierdiscus species are the producers of the marine toxins ciguatoxins and maitotoxins which cause worldwide human intoxications recognized as Ciguatera Fish Poisoning. A deep chemical investigation of a cultured strain of G. belizeanus, collected in the Caribbean Sea, led to the identification of a structural homologue of the recently described gambierone isolated from the same strain. The structure was elucidated mainly by comparison of NMR and MS data with those of gambierone and ascertained by 2D NMR data analyses. Gratifyingly, a close inspection of the MS data of the new 44-methylgambierone suggests that this toxin would actually correspond to the structure of maitotoxin-3 (MTX3, m/z 1039.4957 for the protonated adduct) detected in 1994 in a Pacific strain of Gambierdiscus and recently shown in routine monitoring programs. Therefore, this work provides for the first time the chemical identification of the MTX3 molecule by NMR. Furthermore, biological data confirmed the similar activities of both gambierone and 44-methylgambierone. Both gambierone and MTX3 induced a small increase in the cytosolic calcium concentration but only MTX3 caused cell cytotoxicity at micromolar concentrations. Moreover, chronic exposure of human cortical neurons to either gambierone or MTX3 altered the expression of ionotropic glutamate receptors, an effect already described before for the synthetic ciguatoxin CTX3C. However, even when gambierone and MTX3 affected glutamate receptor expression in a similar manner their effect on receptor expression differed from that of CTX3C, since both toxins decreased AMPA receptor levels while increasing N-methyl-d-aspartate (NMDA) receptor protein. Thus, further studies should be pursued to clarify the similarities and differences in the biological activity between the known ciguatoxins and the new identified molecule as well as its contribution to the neurological symptoms of ciguatera.

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Section: Introductionmentioning

confidence: 99%

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus

Boente-Juncal

Alvarez²,

Antelo³

et al. 2019

Toxins

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“…Furthermore, CTXs may undergo structural modifications that can increase or decrease their toxicity [51], and this would need to be further evaluated for the gambierones. Also, the sensitivity/bioactivity of CTXs varies between NaV isoforms, which may be differentially expressed between different tissues and organisms [52]; this likely applies to gambierone as well. Data regarding the bioaccumulation, biotransformation, and toxicology of gambierones is needed to fully understand whether these compounds contribute to CP or any toxicological effects both in vitro and in vivo.…”

Section: Role Of Gambierones and C Palmyrensis In Cpmentioning

confidence: 99%

Gambierone and Sodium Channel Specific Bioactivity Are Associated with the Extracellular Metabolite Pool of the Marine Dinoflagellate Coolia palmyrensis

et al. 2023

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Tropical epibenthic dinoflagellate communities produce a plethora of bioactive secondary metabolites, including the toxins ciguatoxins (CTXs) and potentially gambierones, that can contaminate fishes, leading to ciguatera poisoning (CP) when consumed by humans. Many studies have assessed the cellular toxicity of causative dinoflagellate species to better understand the dynamics of CP outbreaks. However, few studies have explored extracellular toxin pools which may also enter the food web, including through alternative and unanticipated routes of exposure. Additionally, the extracellular exhibition of toxins would suggest an ecological function and may prove important to the ecology of the CP-associated dinoflagellate species. In this study, semi-purified extracts obtained from the media of a Coolia palmyrensis strain (DISL57) isolated from the U.S. Virgin Islands were assessed for bioactivity via a sodium channel specific mouse neuroblastoma cell viability assay and associated metabolites evaluated by targeted and non-targeted liquid chromatography tandem and high-resolution mass spectrometry. We found that extracts of C. palmyrensis media exhibit both veratrine enhancing bioactivity and non-specific bioactivity. LC-HR-MS analysis of the same extract fractions identified gambierone and multiple undescribed peaks with mass spectral characteristics suggestive of structural similarities to polyether compounds. These findings implicate C. palmyrensis as a potential contributor to CP and highlight extracellular toxin pools as a potentially significant source of toxins that may enter the food web through multiple exposure pathways.

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“…In fact, the presence of Gambierdiscus species and the related toxins and CFP intoxications have been repeatedly identified in Europe during the last decades, especially in the Canary Islands [1,2] and Madeira [3]. Besides ciguatoxins, which can cause long term neurological complications in humans as a consequence of their permanent activation voltage-gated sodium channels [4][5][6], the structure of an additional ciguatoxin-related toxin named 44-methylgambierone (MTX3) has been recently elucidated [7]. Initial studies on the biological activity of 44methylgambierone described an effect similar to that of the synthetic ciguatoxin CTX3C although of much lower potency [7].…”

Section: Daily Oral Doses Of Ctx3c and Mtx3 For 28 Days Did Not Altered Enzyme Blood Levels Of Swiss Micementioning

confidence: 99%

Effects of synthetic ciguatoxin CTX3C and 44-methylgambierone (MTX3) on voltage-gated sodium channels and their in vivo toxicity

Vale

Boente-Juncal

Raposo-García

et al. 2021

Proceedings of 1st International Electronic Conference on Toxins

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Pharmacology of ciguatoxins

Cited by 4 publications

References 93 publications

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus

Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus

Gambierone and Sodium Channel Specific Bioactivity Are Associated with the Extracellular Metabolite Pool of the Marine Dinoflagellate Coolia palmyrensis

Effects of synthetic ciguatoxin CTX3C and 44-methylgambierone (MTX3) on voltage-gated sodium channels and their in vivo toxicity

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