{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T07:19:42Z","timestamp":1777447182497,"version":"3.51.4"},"reference-count":28,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2019,4,13]],"date-time":"2019-04-13T00:00:00Z","timestamp":1555113600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxins"],"abstract":"<jats:p>Ciguatera Fish Poisoning is a worldwide concern caused by the consumption of fish contaminated with ciguatoxins not only in endemic regions in the Pacific Ocean or the Caribbean Sea but also in emerging areas of Macaronesia on the eastern Atlantic. The recent emergence of these toxins in other coastal areas worldwide, prompted the need for the characterization of the risk in these areas. This Ciguatera Fish Poisoning risk has been recently identified as a potential threat in subtropical areas of the Atlantic coast and scientific efforts are being focused in the identification and confirmation of the toxins involved in this potential risk. Neuroblastoma cell assay has been widely used for the evaluation of the toxicity in several marine biotoxin groups, and found to be a very useful tool for toxicity screening. LC-MS\/MS has been also used for confirmatory purposes although the main limitation of the advances on LC-MS\/MS development is due to commercial unavailability of reference materials and hampers method implementation and validation or even confirmation of the ciguatoxins (CTXs) responsible for the toxic profiles. While neuroblastoma cell assay (N2a) is typically used for toxicity screening as mentioned above, being necessary to confirm this N2a toxicity by LC-MS\/MS, this study is designed using N2a as a tool to confirm the toxicity of the fractions obtained corresponding to potential CTXs analogues according to the analysis by LC-MS\/MS. With this aim, an amberjack sample (Seriola fasciata) from Selvagen Islads (Portugal) and implicated in Ciguatera Fish Poisoning was analyzed by LC-MS\/MS and Caribbean Ciguatoxins were found to be mainly responsible for the toxicity. N2a was used in this work as a tool to help in the confirmation of the toxicity of fractions obtained by HPLC. Caribbean Ciguatoxin-1 was found as the main analogue responsible for the N2a toxicity while three Caribbean Ciguatoxin-1 (C-CTX1) metabolites which contribute to the total toxicity were also identified.<\/jats:p>","DOI":"10.3390\/toxins11040221","type":"journal-article","created":{"date-parts":[[2019,4,15]],"date-time":"2019-04-15T11:15:58Z","timestamp":1555326958000},"page":"221","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":38,"title":["An Attempt to Characterize the Ciguatoxin Profile in Seriola fasciata Causing Ciguatera Fish Poisoning in Macaronesia"],"prefix":"10.3390","volume":"11","author":[{"given":"Pablo","family":"Estevez","sequence":"first","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Castro","sequence":"additional","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Peque\u00f1o-Valtierra","sequence":"additional","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2260-5281","authenticated-orcid":false,"given":"Jos\u00e9","family":"Leao","sequence":"additional","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"},{"name":"European Union Reference Laboratory for Marine Biotoxins, CITEXVI, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oscar","family":"Vilari\u00f1o","sequence":"additional","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"},{"name":"European Union Reference Laboratory for Marine Biotoxins, CITEXVI, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge","family":"Diog\u00e8ne","sequence":"additional","affiliation":[{"name":"IRTA, Marine and Continental Waters, Ctra. Poble Nou, km. 5.5, E-43540 Sant Carles de la R\u00e0pita, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ana","family":"Gago-Mart\u00ednez","sequence":"additional","affiliation":[{"name":"University of Vigo, Department of Analytical and Food Chemistry, Campus Universitario de Vigo, 36310 Vigo, Spain"},{"name":"European Union Reference Laboratory for Marine Biotoxins, CITEXVI, Campus Universitario de Vigo, 36310 Vigo, Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,4,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1267","DOI":"10.1126\/science.155.3767.1267","article-title":"Ciguatoxin: Isolation and chemical nature","volume":"155","author":"Scheuer","year":"1967","journal-title":"Science"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1897","DOI":"10.1021\/cr00021a011","article-title":"Marine toxins","volume":"93","author":"Yasumoto","year":"1993","journal-title":"Chem. Rev."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.2331\/suisan.43.1021","article-title":"Finding of a Dinoflagellate as a Likely Culprit of Ciguatera","volume":"43","author":"Yasumoto","year":"1977","journal-title":"Nippon Suisan Gakkaishi"},{"key":"ref_4","first-page":"615","article-title":"Origin and transfer of toxins involved in ciguatera","volume":"106","author":"Lewis","year":"1993","journal-title":"Comp. Biochem. Physiol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/j.cofs.2017.10.004","article-title":"Analytical challenges to ciguatoxins","volume":"18","author":"Suzuki","year":"2017","journal-title":"Curr. Opin. Food Sci."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"8929","DOI":"10.1021\/ja00206a032","article-title":"Structures of ciguatoxin and its congener","volume":"111","author":"Murata","year":"1989","journal-title":"J. Am. Chem. Soc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"4988","DOI":"10.1021\/ja9944204","article-title":"Structural elucidation of ciguatoxin congeners by fast-atom bombardment tandem mass spectroscopy","volume":"122","author":"Yasumoto","year":"2000","journal-title":"J. Am. Chem. Soc."},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Ikehara, T., Kuniyoshi, K., Oshiro, N., and Yasumoto, T. (2017). Biooxidation of Ciguatoxins Leads to Species-Specific Toxin Profiles. Toxins, 9.","DOI":"10.3390\/toxins9070205"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"656","DOI":"10.1016\/j.toxicon.2009.05.036","article-title":"Ciguatera incidence and fish toxicity in Okinawa, Japan","volume":"56","author":"Oshiro","year":"2010","journal-title":"Toxicon"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"8886","DOI":"10.1021\/ac200799j","article-title":"Detailed LC-MS\/MS Analysis of Ciguatoxins Revealing Distinct Regional and Species Characteristics in Fish and Causative Alga from the Pacific","volume":"83","author":"Yogi","year":"2011","journal-title":"Anal. Chem."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.chroma.2018.08.008","article-title":"Detection of pacific ciguatoxins using liquid chromatography coupled to either low or high resolution mass spectrometry (LC-MS\/MS)","volume":"1571","author":"Sibat","year":"2018","journal-title":"J. Chromatogr."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Ware, G.W. (2001). Ciguatera Fish Poisoning in the Caribbean Islands and Western Atlantic. Reviews of Environmental Contamination and Toxicology: Continuation of Residue Reviews, Springer.","DOI":"10.1007\/978-1-4613-0159-2"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"889","DOI":"10.1016\/S0041-0101(96)00191-2","article-title":"Isolation and characterisation of Caribbean ciguatoxins from the horse-eye jack (Caranx latus)","volume":"35","author":"Vernoux","year":"1997","journal-title":"Toxicon"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"5914","DOI":"10.1021\/ja980389e","article-title":"Structure of Caribbean Ciguatoxin Isolated from Caranx latus","volume":"120","author":"Lewis","year":"1998","journal-title":"J. Am. Chem. Soc."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"192","DOI":"10.1016\/j.foodchem.2011.08.059","article-title":"Caribbean ciguatoxin profile in raw and cooked fish implicated in ciguatera","volume":"131","author":"Abraham","year":"2012","journal-title":"Food Chem."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1852","DOI":"10.1002\/etc.4137","article-title":"Ciguatoxin prevalence in 4 commercial fish species along an oceanic exposure gradient in the US Virgin Islands","volume":"37","author":"Loeffler","year":"2018","journal-title":"Environ. Toxicol. Chem."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/S0041-0101(02)00088-0","article-title":"Characterisation of multiple Caribbean ciguatoxins and congeners in individual specimens of horse-eye jack (Caranx latus) by high-performance liquid chromatography\/mass spectrometry","volume":"40","author":"Pottier","year":"2002","journal-title":"Toxicon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1016\/j.toxicon.2003.09.004","article-title":"Identification of slow and fast-acting toxins in a highly ciguatoxic barracuda (Sphyraena barracuda) by HPLC\/MS and radiolabelled ligand binding","volume":"42","author":"Pottier","year":"2003","journal-title":"Toxicon"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ciguatoxin Group (2010). Pannel on Contaminants in the Food Chain Scientific Opinion on marine biotoxins in shellfish\u2014Emerging toxins. EFSA J., 8, 1627.","DOI":"10.2903\/j.efsa.2010.1627"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6032","DOI":"10.1021\/ac100516q","article-title":"First Toxin Profile of Ciguateric Fish in Madeira Arquipelago (Europe)","volume":"82","author":"Otero","year":"2010","journal-title":"Anal. Chem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1516","DOI":"10.1016\/j.toxicon.2010.07.021","article-title":"Ciguatera fish poisoning on the West Africa Coast: An emerging risk in the Canary Islands (Spain)","volume":"56","author":"Boada","year":"2010","journal-title":"Toxicon"},{"key":"ref_22","doi-asserted-by":"crossref","unstructured":"Costa, P.R., Estevez, P., Castro, D., Soli\u00f1o, L., Gouveia, N., Santos, C., Rodrigues, S.M., Leao, J.M., and Gago-Mart\u00ednez, A. (2018). New Insights into the Occurrence and Toxin Profile of Ciguatoxins in Selvagens Islands (Madeira, Portugal). Toxins, 10.","DOI":"10.3390\/toxins10120524"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1059","DOI":"10.1002\/jms.4281","article-title":"Design of experiments for the optimization of electrospray ionization in the LC-MS\/MS analysis of ciguatoxins","volume":"53","author":"Moreiras","year":"2018","journal-title":"J. Mass. Spectrom."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.foodchem.2018.12.038","article-title":"Implementation of liquid chromatography tandem mass spectrometry for the analysis of ciguatera fish poisoning in contaminated fish samples from Atlantic coasts","volume":"280","author":"Estevez","year":"2019","journal-title":"Food Chem."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1000","DOI":"10.1080\/19440049.2012.660707","article-title":"Towards the standardisation of the neuroblastoma (neuro-2a) cell-based assay for ciguatoxin-like toxicity detection in fish: Application to fish caught in the Canary Islands","volume":"29","author":"Caillaud","year":"2012","journal-title":"Food Addit. Contam. Part"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.toxicon.2009.09.008","article-title":"Ciguatera: A public health perspective","volume":"56","author":"Dickey","year":"2010","journal-title":"Toxicon"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"190","DOI":"10.1006\/abio.1993.1476","article-title":"Tetrazolium-Based Cell Bioassay for Neurotoxins Active on Voltage-Sensitive Sodium Channels: Semiautomated Assay for Saxitoxins, Brevetoxins, and Ciguatoxins","volume":"214","author":"Manger","year":"1993","journal-title":"Anal. Biochem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1093\/jaoac\/78.2.521","article-title":"Detection of sodium channel toxins: Directed cytotoxicity assays of purified ciguatoxins, brevetoxins, saxitoxins, and seafood extracts","volume":"78","author":"Manger","year":"1995","journal-title":"J. AOAC Int."}],"container-title":["Toxins"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/221\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:45:18Z","timestamp":1760186718000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6651\/11\/4\/221"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,4,13]]},"references-count":28,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2019,4]]}},"alternative-id":["toxins11040221"],"URL":"https:\/\/doi.org\/10.3390\/toxins11040221","relation":{},"ISSN":["2072-6651"],"issn-type":[{"value":"2072-6651","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,4,13]]}}}