Добірка наукової літератури з теми "Pinnatoxines"

Over the year 2018, we assessed toxin contamination of shellfish collected on a monthly basis in Ingril Lagoon, France, a site known as a hotspot for Vulcanodinium rugosum growth. This short time-series study gave an overview of the presence and seasonal variability of pinnatoxins, pteriatoxins, portimines and kabirimine, all associated with V. rugosum, in shellfish. Suspect screening and targeted analysis approaches were implemented by means of liquid chromatography coupled to both low- and high-resolution mass spectrometry. We detected pinnatoxin-A and pinnatoxin-G throughout the year, with maximum levels for each one observed in June (6.7 µg/kg for pinnatoxin-A; 467.5 µg/kg for pinnatoxin-G), whereas portimine-A was detected between May and September (maximum level = 75.6 µg/kg). One of the main findings was the identification of a series of fatty acid esters of pinnatoxin-G (n = 13) although the levels detected were low. The profile was dominated by the palmitic acid conjugation of pinnatoxin-G. The other 12 fatty acid esters had not been reported in European shellfish to date. In addition, after thorough investigations, two compounds were detected, with one being probably identified as portimine-B, and the other one putatively attributed to pteriatoxins. If available, reference materials would have ensured full identification. Monitoring of these V. rugosum emerging toxins and their biotransformation products will contribute towards filling the data gaps pointed out in risk assessments and in particular the need for more contamination data for shellfish.

For the first time, pinnatoxins have been detected in shellfish from the Atlantic and Cantabrian coasts of Spain. High sensitivity LC-MS/MS systems were used to monitor all the currently known pinnatoxins (A–H). Pinnatoxin G (PnTX G) was the most prevalent toxin of the group, but its metabolite PnTX A has also been found at much lower levels. No trend in PnTX G concentration was found in the area, but a hotspot in the Ría de Camariñas has been identified. The maximum concentrations found did not exceed 15 µg·kg−1, being, in most cases, below 3 µg·kg−1. The highest concentrations were found in wild (intertidal) populations of mussels which attained much higher levels than raft-cultured ones, suggesting that the toxin-producer organisms preferentially develop in shallow areas. Other bivalve species had, in general, lower concentrations. The incidence of PnTX G followed a seasonal pattern in which the maximum concentrations took place in winter months. PnTX G was found to be partially esterified but the esterification percentage was not high (lower than 30%).

Seafood represents a significant part of the human staple diet. In the recent years, the identification of emerging lipophilic marine toxins has increased, leading to the potential for consumers to be intoxicated by these toxins. In the present work, we investigate the presence of lipophilic marine toxins (both regulated and emerging) in commercial seafood products from non-European locations, including mussels Mytilus chilensis from Chile, clams Tawerea gayi and Metetrix lyrate from the Southeast Pacific and Vietnam, and food supplements based on mussels formulations of Perna canaliculus from New Zealand. All these products were purchased from European Union markets and they were analyzed by UPLC-MS/MS. Results showed the presence of the emerging pinnatoxin-G in mussels Mytilus chilensis at levels up to 5.2 µg/kg and azaspiracid-2 and pectenotoxin-2 in clams Tawera gayi up to 4.33 µg/kg and 10.88 µg/kg, respectively. This study confirms the presence of pinnatoxins in Chile, one of the major mussel producers worldwide. Chromatograms showed the presence of 13-desmethyl spirolide C in dietary supplements in the range of 33.2–97.9 µg/kg after an extraction with water and methanol from 0.39 g of the green lipped mussels powder. As far as we know, this constitutes the first time that an emerging cyclic imine toxin in dietary supplements is reported. Identifying new matrix, locations, and understanding emerging toxin distribution area are important for preventing the risks of spreading and contamination linked to these compounds.

Spirolides (SPXs), gymnodimines (GYMs), and pinnatoxins (PnTXs) have been detected in shellfish from the northwestern Mediterranean coast of Spain. Several samples of bivalves were collected from Fangar Bay and Alfacs Bay in Catalonia over a period of over 7 years (from 2015 to 2021). Shellfish samples were analyzed for cyclic imines (CIs) on an LC1200 Agilent and 3200 QTrap triple–quadrupole mass spectrometer. In shellfish, SPX-1 was detected in two cases (of 26.5 µg/kg and 34 µg/kg), and GYM-A was only detected in trace levels in thirteen samples. Pinnatoxin G (PnTX-G) was detected in 44.6% of the samples, with its concentrations ranging from 2 µg/kg to 38.4 µg/kg. Statistical analyses revealed that seawater temperature influenced the presence or absence of these toxins. PnTX-G showed an extremely significant presence/temperature relationship in both bays in comparison to SPX-1 and GYM-A. The prevalence of these toxins in different bivalve mollusks was evaluated. A seasonal pattern was observed, in which the maximum concentrations were found in the winter months for SPX-1 and GYM-A but in the summer months for PnTX-G. The obtained results indicate that it is unlikely that CIs in the studied area pose a potential health risk through the consumption of a seafood diet. However, further toxicological information about CIs is necessary in order to perform a conclusive risk assessment.

Cyclic imines are a class of lipophilic shellfish toxins comprising gymnodimines, spirolides, pinnatoxins, portimines, pteriatoxins, prorocentrolides, spiro-prorocentrimine, symbiomines and kabirimine. They are structurally diverse, but all share an imine moiety as part of a bicyclic ring system. These compounds are produced by marine microalgal species and are characterized by the rapid death that they induce when injected into mice. Cyclic imines have been detected in a range of shellfish species collected from all over the world, which raises the question as to whether they present a food safety risk. The European Food Safety Authority (EFSA) considers them to be an emerging food safety issue, and in this review, the risk posed by these toxins to shellfish consumers is assessed by collating all available occurrence and toxicity data. Except for pinnatoxins, the risk posed to human health by the cyclic imines appears low, although this is based on only a limited dataset. For pinnatoxins, two different health-based guidance values have been proposed at which the concentration should not be exceeded in shellfish (268 and 23 µg PnTX/kg shellfish flesh), with the discrepancy caused by the application of different uncertainty factors. Pinnatoxins have been recorded globally in multiple shellfish species at concentrations of up to 54 times higher than the lower guidance figure. Despite this observation, pinnatoxins have not been associated with recorded human illness, so it appears that the lower guidance value may be conservative. However, there is insufficient data to generate a more robust guidance value, so additional occurrence data and toxicity information are needed.

Pinnatoxin G (PnTx-G) is a marine cyclic imine toxin produced by the dinoflagellate Vulcanodinium rugosum, frequently detected in edible shellfish from Ingril Lagoon (France). As other pinnatoxins, to date, no human poisonings ascribed to consumption of PnTx-G contaminated seafood have been reported, despite its potent antagonism at nicotinic acetylcholine receptors and its high and fast-acting toxicity after intraperitoneal or oral administration in mice. The hazard characterization of PnTx-G by oral exposure is limited to a single acute toxicity study recording lethality and clinical signs in non-fasted mice treated by gavage or through voluntary food ingestion, which showed differences in PnTx-G toxic potency. Thus, an acute toxicity study was carried out using 3 h-fasted CD-1 female mice, administered by gavage with PnTx-G (8–450 µg kg−1). At the dose of 220 µg kg−1 and above, the toxin induced a rapid onset of clinical signs (piloerection, prostration, hypothermia, abdominal breathing, paralysis of the hind limbs, and cyanosis), leading to the death of mice within 30 min. Except for moderate mucosal degeneration in the small intestine recorded at doses of 300 µg kg−1, the toxin did not induce significant morphological changes in the other main organs and tissues, or alterations in blood chemistry parameters. This acute oral toxicity study allowed to calculate an oral LD50 for PnTx-G equal to 208 μg kg−1 (95% confidence limits: 155–281 µg kg−1) and to estimate a provisional NOEL of 120 µg kg−1.

Les efflorescences phytoplanctoniques nuisibles et/ou toxiques impactent depuis très longtemps les écosystèmes marins du monde entier. Ces développements massifs ont un effet néfaste sur les écosystèmes et leur exploitation. Les lagunes du Languedoc-Roussillon sont touchées depuis plusieurs décennies. En plus des risques sanitaires récurrents dus aux genres Dinophysis (toxines DSP) et Alexandrium (toxines PSP), Vulcanodinium rugosum a été identifiée en 2011 dans la lagune d’Ingril. Cette nouvelle espèce est productrice de pinnatoxines (neurotoxines). A travers ces travaux de thèse, la biologie de cette nouvelle espèce (cycle de vie, condition de croissance, production de toxines), ses capacités de contamination des mollusques et sa distribution géographique dans les lagunes limitrophes ont été étudiées sur des cultures au laboratoire et via des suivis environnementaux.Les résultats de cette étude ont mis en évidence le caractère thermophile et euryhalin de cette microalgue (croissance optimale à 25°C et à une salinité de 40 ) avec des plages de croissance comprises entre 20 et 30°C. Sa capacité à croître sur une source azotée organique (urée) a été observée in vitro. Son expansion à des lagunes du Languedoc-Roussillon autre que l’étang d’Ingril, a été confirmée par la mise en évidence de la contamination des moules par la pinnatoxine G. La survie de ce dinoflagellé dans le tractus digestif des moules et des huîtres prouve que le transfert de coquillages est une source de contamination potentielle des écosystèmes non impactés par cette espèce toxique.Le cycle de vie de V. rugosum n’a pu être élucidé que partiellement, le kyste de résistance n’ayant pas été identifié formellement. Les kystes temporaires apparaissent comme des stades très importants à prendre en considération en raison de leur capacité à se diviser et de leur forte présence sur les macrophytes. Ces formes temporaires de résistance peuvent constituer une source de contamination non négligeable des mollusques dans la lagune de l’Ingril même lorsque les cellules végétatives de V. rugosum sont peu présentes dans la colonne d’eau. En raison des faibles densités de V. rugosum in situ et la difficulté de son identification sur des critères morphologique, sa surveillance dans le cadre du REPHY demeure difficile. Ainsi l’utilisation de systèmes d’échantillonnage passifs (SPATT) constitués de résines qui adsorbent les toxines dissoutes dans l’eau permettrait la détection précoce des toxines associées à ces espèces benthiques émergentes. Cette étude met en évidence la prolifération d’une espèce émergente thermophile qui pourrait avec d’autres et à la faveur de changements climatiques constituer des problèmes sanitaires et économiques importants dans les écosystèmes lagunaires vulnérables de la Méditerranée
Harmful and / or toxic phytoplankton blooms impact for a long time marine ecosystems worldwide. These massive developments have an adverse effect on ecosystems and their exploitation. The lagoons of the region Languedoc-Roussillon are affected for decades. In addition to recurring health risks from Dinophysis (DSP toxins) and Alexandrium (PSP toxins), Vulcanodinium rugosum was identified in 2011 in the lagoon Ingril. This new species product pinnatoxins (neurotoxins). Through this thesis work, the biology of this new species (life cycle, growth condition, toxin production), its shellfish contamination capacity and geographic distribution in neighboring lagoons were studied on cultures in the laboratory and via environmental monitoring.The results of this study have demonstrated its thermophilic and euryhaline features (optimum salinity and temperature of 25°C and 40 respectively) and its growth ranges between 20 and 30°C. Its ability to grow on an organic nitrogen source (urea) has been showed in vitro. Its expansion in other lagoons of Languedoc-Roussillon, was confirmed by the contamination of the mussels by the pinnatoxin G. The survival of this organism in the digestive tract of mussels and oysters proves that the transfer of shellfish is potentially a source of contamination of new ecosystems not yet affected by this toxic species.The life cycle of V. rugosum has not been fully described because the resistance cyst has not been formally identified. Temporary cysts appear as very important stages to be considered because of their ability to divide and their strong presence on macrophytes. These temporary forms of resistance may be a significant source of contamination of shellfish in the lagoon of the Ingril even when the vegetative cells of V. rugosum are weakly present in the water column. Because of the low densities of V. rugosum in situ and the difficulty of its identification on morphological criteria, the monitoring within the REPHY protocol remains difficult. Thus the use of passive sampling systems (Spatt) made with resins which adsorb toxins dissolved in water would make possible the early detection of toxins associated with these emerging benthic species. This study highlights the growth of an emerging thermophilic species that might with others and thanks to climate change provide important health and economic problems in vulnerable lagoon ecosystems of the Mediterranean

Les efflorescences phytoplanctoniques nuisibles ont des impacts croissants sur les écosystèmes et sur les populations humaines. Dans un contexte de réchauffement des eaux et des océans, elles sont au cœur des problématiques liant santé de l’environnement, des animaux et des humains. Ces travaux s’articulent autour de la microalgue toxique Vulcanodinium rugosum productrice de pinnatoxines (PnTX) et de portimines (Prtn). Ces toxines s’accumulent dans les organismes marins et sont fréquemment détectées dans le monde et plus particulièrement dans les lagunes méditerranéennes françaises. Les objectifs de ces travaux étaient d’évaluer la distribution de la microalgue en lien avec les conditions environnementales dans quatre lagunes méditerranéennes françaises, la contamination de divers organismes marins par la PnTX G et la Prtn A, et les impacts écologiques et risques sanitaires associés.Nous avons développé une méthode sensible et spécifique pour détecter les cellules de Vulcanodinium rugosum basée sur des substrats artificiels couplés à de la qPCR (SA-qPCR). Notre campagne terrain a montré que la microalgue et les toxines étaient présentes dans toutes les lagunes étudiées et qu’elles pouvaient contaminer des espèces marines incluant mollusques bivalves, poissons, gastéropodes et échinodermes. Les dynamiques spatiotemporelles de la microalgue et des toxines dans les moules ont été liées à des variations saisonnières de facteurs environnementaux. Une approche basée sur la modélisation à partir de paramètres environnementaux a permis d’évaluer les risques pour les populations humaines selon les périodes de l’année. Plus de 25 % des consommateurs de produits de la mer dépassaient la valeur repère aigüe provisoire en été à Ingril et à Vic. Nous n’avons pas observé d’impact de l’exposition des juvéniles de mulets à Vulcanodinium rugosum, mais cette espèce pourrait disséminer la microalgue au sein des lagunes via un transport par le tractus intestinal. Enfin, Les concentrations en PnTX G et en Prtn A détectées dans les huîtres in situ peuvent être liées à une longue exposition, et la PnTX G persiste longtemps dans les tissus des mollusques bivalves.Ces travaux ont fourni des connaissances sur les impacts de Vulcanodinium rugosum sur les écosystèmes et sur l’homme. Les informations et outils utilisés devraient être d’un grand intérêt pour les gestionnaires de la surveillance du milieu marin. Les études ont également mené à des questions concernant l’expansion de cette microalgue à d’autres écosystèmes, les autres espèces potentiellement contaminées, les impacts subléthaux sur les organismes marins, et la toxicité chronique pour l’homme. Ils montrent l’importance de poursuivre des travaux portant sur ce dinoflagellé et ces toxines, notamment dans le contexte d’un réchauffement des eaux favorisant les efflorescences à l’échelle globale
Harmful phytoplankton blooms have growing impacts on ecosystems and human populations. In the context of warming waters and oceans, they are one of the main issues linking environmental, animal and human health. This research focuses on the toxic microalga Vulcanodinium rugosum, which produces pinnatoxins (PnTX) and portimines (Prtn). These toxins accumulate in marine organisms and are frequently detected worldwide, particularly in French Mediterranean lagoons. The objectives were to study the microalga distribution in relationship with environmental conditions in four French Mediterranean lagoons, the contamination by PnTX G and Prtn A of various marine organisms, the ecological impacts and the health risks.At first, we developed a sensitive and specific methodology for detecting Vulcanodinium rugosum cells in marine environments, based on artificial substrates coupled with qPCR (AS-qPCR). The results of our field campaign showed that microalgae and toxins were present in all studied lagoons, and that they could contaminate a wide variety of marine species including bivalve molluscs, fish, gastropods and echinoderms. The spatiotemporal dynamics of microalgae and toxins in mussels were linked to seasonal variations in temperature and other hydrochemical factors. A modeling approach based on environmental parameters enabled us to assess the risks to human populations at different times of the year. We estimated that over 25 % of seafood consumers exceeded the provisional acute benchmark value in summer at Ingril and Vic. We did not observe any impact of mullet juvenile exposure to Vulcanodinium rugosum, but this species could be involved in the expansion of the microalga within the lagoons via transport through the intestinal tract. Finally, the kinetics of contamination and elimination in oysters showed that high concentrations could be linked to long-term exposure, and that PnTX G persisted for a long time in bivalve molluscs’ tissues.This work provided therefore important knowledge on the impacts of Vulcanodinium rugosum on ecosystems and humans. The information and tools developed should be of great interest to environmental and health monitoring managers. This study also led to questions concerning the general expansion of Vulcanodinium rugosum area, other species that could possibly be contaminated, sub-lethal impacts on marine organisms, and the chronic risks to humans inherent in persistent contamination in seafood products. They therefore show the importance of studies focusing on this dinoflagellate and its toxins, particularly in the context of warming waters favoring blooms on a global scale

Thesis (M.S.)--Florida State University, 2006.
Advisor: Armen Zakarian, Florida State University, College of Arts and Sciences, Dept. of Chemistry. Title and description from dissertation home page (viewed Sept. 19, 2006). Document formatted into pages; contains xiv, 120 pages. Includes bibliographical references.

( + )-Pinnatoxin A 3, isolated from the shellfish Pinna muricata, is thought to be a calcium channel activator. A key transformation in the synthesis of 3 reported (J. Am. Chem. Soc . 2008, 130, 3774) by Armen Zakarian, now at the University of California, Santa Barbara, was the diastereoselective Claisen rearrangement of 1 to 2. The alcohol portion of ester 1 was derived from the aldehyde 4, prepared from D-ribose. The absolute configuration of the secondary allylic alcohol was established by chiral amino alcohol catalyzed addition of diethyl zinc to the unsaturated aldehyde 5. The acid portion of the ester 1 was prepared from (S)-citronellic acid, by way of the Evans imide 7. Methylation proceeded with high diasterocontrol, to give 8. Functional group manipulation provided the imide 9. Alkylation then led to 10, again with high diastereocontrol. In each case, care had to be taken in the further processing of the α-chiral acyl oxazolidinones. Direct NaBH4 reduction of 8 delivered the primary alcohol. To prepare the acid 10, the alkylated acyl oxazolidinone was hydrolyzed with alkaline hydrogen peroxide. On exposure of the ester 1 to the enantiomerically-pure base 11, rearrangement proceeded with high diastereocontrol, to give the acid 2. This outcome suggests that deprotonation proceeded to give the single geometric form of the enolate, that was then trapped to give specifically the ketene silyl acetal 12. This elegant approach is dependent on both the ester 1 and the base 11 being enantiomerically pure. The carbocyclic ring of pinnatoxin A 3 was assembled by intramolecular aldol condensation of the dialdehyde 11. This outcome was remarkable, in that 11 is readily epimerizable, and might also be susceptible to β-elimination. Note that the while the diol corresponding to 11 could be readily oxidized to 11 under Swern conditions, attempts to oxidize the corresponding hydroxy aldehyde were not fruitful.