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This research was supported by the Ministerio de Ciencia e Innovacion (MICIN) and the Agencia Estatal de Investigacion (AEI) (Spain) through the CELLECTRA (PID2020-112976RB-C21 and PID2020-112976RB-C22) project. J.R. acknowledges IRTA for his PhD grant (CPI0422). A.S.-H. acknowledges the Canary Islands Research Agency (ACIISI) for his research staff training aid through the Catalina Ruiz Program (APCR2022010011). The authors also acknowledge the support from the CERCA Program/Generalitat de Catalunya.

Analysis of institutional authors

Reverté, JaumeAuthorRambla-Alegre, MariaAuthorDiogene, JorgeAuthorCampas, MonicaCorresponding Author

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August 18, 2024
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Toxicity Equivalency Factors for Tetrodotoxin Analogues Determined with Automated Patch Clamp on Voltage-Gated Sodium Channels in Neuro-2a Cells

Publicated to:Journal Of Agricultural And Food Chemistry. 72 (32): 18192-18200 - 2024-08-05 72(32), DOI: 10.1021/acs.jafc.4c04321

Authors: Reverte, Jaume; Rambla-Alegre, Maria; Sanchez-Henao, Andres; Mandalakis, Manolis; Peristeraki, Panagiota; Molgo, Jordi; Diogene, Jorge; Sureda, Francesc X; Campas, Monica

Affiliations

Aigües Marines i Continentals. Producció Animal - Author
Hellen Ctr Marine Res HCMR, Inst Marine Biol Biotechnol & Aquaculture, Iraklion 71003, Greece - Author
Hellen Ctr Marine Res HCMR, Inst Marine Biol Resources & Inland Waters, Iraklion 71003, Greece - Author
IRTA, Ctra, La Rapita 43540, Spain - Author
Univ Las Palmas Gran Canaria, Univ Inst Anim Hlth & Food Safety IUSA, Arucas 35416, Spain - Author
Univ Paris Saclay, French Alternat Energies & Atom Energy Commiss CE, INRAE, DMTS,SIMoS,EMR CNRS 9004, F-91191 Gif Sur Yvette, France - Author
Univ Rovira & Virgili URV, Fac Med & Hlth Sci, Basic Med Sci Dept, Reus 43201, Spain - Author
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Abstract

Tetrodotoxin (TTX) is a potent marine neurotoxin, responsible for numerous poisoning incidents and some human fatalities. To date, more than 30 TTX analogues have been identified, but their individual toxicities and roles in poisoning remain largely unknown. In this work, the toxicity equivalency factors (TEFs) of five TTX analogues were determined by assessing the blockade of voltage-gated sodium channels in Neuro-2a cells using automated patch clamp (APC). All TTX analogues were less toxic than TTX. The derived TEFs were applied to the individual TTX analogues concentrations measured in pufferfish samples, using liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS). A comparison of these results with those obtained from APC analysis demonstrated that TEFs can be effectively used to translate LC-MS/MS analytical data into meaningful toxicological information. This is the first study to utilize APC device for the toxicological assessment of TTX analogues, highlighting its potential as a bioanalytical tool for seafood safety management and human health protection.

Keywords

AnimalsAssayBrevetoxinsCell lineChromatography, liquidFood safetFood safetyHumansLagocephalus-sceleratus gmelinMiceNiphoblesPatch-clamp techniquesPuffer fishPufferfishSaxitoxinsSeafoodSingle-cell analysisSingle-cellanalysisTandem mass spectrometryTetraodontiformesTetrodotoxinTetrodotoxin analogueToxicologyTtVoltage-gated sodium channels

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Journal Of Agricultural And Food Chemistry due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2024 there are still no calculated indicators, but in 2023, it was in position 7/94, thus managing to position itself as a Q1 (Primer Cuartil), in the category Agriculture, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-09-08:

  • WoS: 2
  • Europe PMC: 2

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-09-08:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 4.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 4 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 2.
  • The number of mentions on the social network X (formerly Twitter): 3 (Altmetric).

It is essential to present evidence supporting full alignment with institutional principles and guidelines on Open Science and the Conservation and Dissemination of Intellectual Heritage. A clear example of this is:

  • The work has been submitted to a journal whose editorial policy allows open Open Access publication.
  • Assignment of a Handle/URN as an identifier within the deposit in the Institutional Repository: http://hdl.handle.net/20.500.12327/3292

Leadership analysis of institutional authors

This work has been carried out with international collaboration, specifically with researchers from: France; Greece.

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (REVERTE NAVARRO, JAUME) and Last Author (CAMPAS HOMS, MONICA).

the author responsible for correspondence tasks has been CAMPAS HOMS, MONICA.