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Mireille Chinain - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Ciguatera and other phycotoxin-related risks in Anaho Bay (Nuku Hiva Island, French Polynesia) : molecular, toxicological, and chemical analyses of passive samplers
Toxins, 2020Co-Authors: Mélanie Roué, Jérôme Viallon, Manoella Sibat, K.f. Smith, K. Henry, A. Ung, L. Biessy, P. Hess, H.t. Darius, Mireille ChinainAbstract:Ciguatera poisoning is a foodborne illness caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates from the genera Gambierdiscus and Fukuyoa. The suitability of Solid Phase Adsorption Toxin Tracking (SPATT) technology for the monitoring of dissolved CTXs in the marine environment has recently been demonstrated. To refine the use of this passive monitoring tool in ciguateric areas, the effects of deployment time and sampler format on the adsorption of CTXs by HP20 resin were assessed in Anaho Bay (Nuku Hiva Island, French Polynesia), a well-known Ciguatera hotspot. Toxicity data assessed by means of the mouse neuroblastoma cell-based assay (CBA-N2a) showed that a 24 h deployment of 2.5 g of resin allowed concentrating quantifiable amounts of CTXs on SPATT samplers. The CTX levels varied with increasing deployment time, resin load, and surface area. In addition to CTXs, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were also detected in SPATT extracts using liquid chromatographycoupled to tandem mass spectrometry (LC-MS/MS), consistent with the presence of Gambierdiscus and Prorocentrum species in the environment, as assessed by quantitative polymerase chain reaction (qPCR) and high-throughput sequencing (HTS) metabarcoding analyses conducted on passive window screen (WS) artificial substrate samples. Although these preliminary findings await further confirmation in follow-up studies, they highlight the usefulness of SPATT samplers in the routine surveillance of CPrisk on a temporal scale, and the monitoring of other phycotoxin-related risks in Ciguatera-prone areas.
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tissue distribution and elimination of ciguatoxins in tridacna maxima tridacnidae bivalvia fed gambierdiscus polynesiensis
Toxins, 2018Co-Authors: Mélanie Roué, Hélène Taiana Darius, André Ung, Jérôme Viallon, Manoella Sibat, Zouher Amzil, Philipp Hess, Mireille ChinainAbstract:Ciguatera is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs). Ciguatera-like poisoning events involving giant clams (Tridacna maxima) are reported occasionally from Pacific islands communities. The present study aimed at providing insights into CTXs tissue distribution and detoxification rate in giant clams exposed to toxic cells of Gambierdiscus polynesiensis, in the framework of seafood safety assessment. In a first experiment, three groups of tissue (viscera, flesh and mantle) were dissected from exposed individuals, and analyzed for their toxicity using the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. The viscera, flesh, and mantle were shown to retain 65%, 25%, and 10% of the total toxin burden, respectively. All tissues reached levels above the safety limit recommended for human consumption, suggesting that evisceration alone, a practice widely used among local populations, is not enough to ensure seafood safety. In a second experiment, the toxin content in contaminated giant clams was followed at different time points (0, 2, 4, and 6 days post-exposure). Observations suggest that no toxin elimination is visible in T. maxima throughout 6 days of detoxification.
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Tectus niloticus (Tegulidae, Gastropod) as a Novel Vector of Ciguatera Poisoning: Clinical Characterization and Follow-Up of a Mass Poisoning Event in Nuku Hiva Island (French Polynesia)
MDPI AG, 2018Co-Authors: Clemence Mahana Iti Gatti, Mélanie Roué, Hélène Taiana Darius, Davide Lonati, Arturo Zancan, Azzurra Schicchi, Carlo Alessandro Locatelli, Mireille ChinainAbstract:Ciguatera fish poisoning (CFP) is the most prevalent non-bacterial food-borne form of poisoning in French Polynesia, which results from the consumption of coral reef fish naturally contaminated with ciguatoxins produced by dinoflagellates in the genus Gambierdiscus. Since the early 2000s, this French territory has also witnessed the emergence of atypical forms of Ciguatera, known as Ciguatera shellfish poisoning (CSP), associated with the consumption of marine invertebrates. In June 2014, nine tourists simultaneously developed a major and persistent poisoning syndrome following the consumption of the gastropod Tectus niloticus collected in Anaho, a secluded bay of Nuku Hiva Island (Marquesas Archipelago, French Polynesia). The unusual nature and severity of this event prompted a multidisciplinary investigation in order to characterize the etiology and document the short/long-term health consequences of this mass-poisoning event. This paper presents the results of clinical investigations based on hospital medical records, medical follow-up conducted six and 20 months post-poisoning, including a case description. This study is the first to describe the medical signature of T. niloticus poisoning in French Polynesia and contributed to alerting local authorities about the potential health hazards associated with the consumption of this gastropod, which is highly prized by local communities in Pacific island countries and territories
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Evidence of the bioaccumulation of ciguatoxins in giant clams (Tridacna maxima) exposed to Gambierdiscus spp. cells
Harmful Algae, 2016Co-Authors: Mélanie Roué, Hélène Taiana Darius, Sandy Picot, André Ung, Jérôme Viallon, Nabila Gaertner-mazouni, Manoella Sibat, Zouher Amzil, Mireille ChinainAbstract:Ciguatera Fish Poisoning (CFP) is a foodborne disease classically related to the consumption of tropical coral reef fishes contaminated with ciguatoxins (CTXs), neurotoxins produced by dinoflagellates of the Gambierdiscus genus. Severe atypical Ciguatera-like incidents involving giant,clams, a marine resource highly consumed in the South Pacific, are also frequently reported in many Pacific Islands Countries and Territories. The present study was designed to assess the ability of giant clams to accumulate CTXs in their tissues and highlight the potential health risks associated with their consumption. Since giant clams are likely to be exposed to both free-swimming Gambierdiscus cells and dissolved CTXs in natural environment, ex situ contamination experiments were conducted as follows: giant clams were exposed to live or lyzed cells of TB92, a highly toxic strain of G. polynesiensis containing 5.83 +/- 0.85 pg P-CTX-3C equiv. cell(-1) vs. HIT0, a weakly toxic strain of G. toxicus containing only (2.05 +/- 1.16) x 10(-3) pg P-CTX-3C equiv. cell-1, administered over a 48 h period at a concentration of 150 cells mL(-1). The presence of CTXs in giant clams tissues was further assessed using the mouse neuroblastoma cell-based assay (CBA-N2a). Results showed that giant clams exposed to either lyzed or live cells of TB92 were able to bioaccumulate CTXs at concentrations well above the safety limit recommended for human consumption, i.e. 3.28 +/- 137 and 2.92 +/- 1.03 ng P-CTX-3C equiv. g(-1) flesh (wet weight), respectively, which represented approximately 3% of the total toxin load administered to the animals. In contrast, giant clams exposed to live or lyzed cells of HIT0 were found to be free of toxins, suggesting that in the nature, the risk of contamination of these bivalves is established only in the presence of highly toxic blooms of Gambierdiscus. Liquid chromatography-mass spectrometry (LC-MS/MS) analyses confirmed CBA-N2a results and also revealed that P-CTX-3B was the major CTX congener retained in the tissues of giant clams fed with TB92 cells. To the best of our knowledge, this study is the first to provide evidence of the bioaccumulation of Gambierdiscus CTX.s in giant clams and confirms that these bivalve molluscs can actually constitute another pathway in Ciguatera poisonings. While most monitoring programs currently focus on fish toxicity, these findings stress the importance of a concomitant surveillance of these marine invertebrates in applicable locations for an accurate assessment of Ciguatera risk.
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protective effect of heliotropium foertherianum boraginaceae folk remedy and its active compound rosmarinic acid against a pacific ciguatoxin
Journal of Ethnopharmacology, 2012Co-Authors: Fanny Rossi, Mireille Chinain, Valerie Jullian, Ralph Pawlowiez, Shilpa Kumarroine, Mohamed Haddad, Taiana H Darius, Nabila Gaertnermazouni, Dominique LaurentAbstract:Abstract Ethnopharmacological relevance Senescent leaves of Heliotropium foertherianum Diane & Hilger (Boraginaceae) are traditionally used in the Pacific region to treat Ciguatera Fish Poisoning. This plant contains rosmarinic acid that is known for its multiple biological activities. In the present study, H. foertherianum aqueous extract, rosmarinic acid and its derivatives were evaluated for their capacity to reduce the effect of ciguatoxins. Materials and methods Aqueous extract of H. foertherianum leaves was prepared and studied for its effects against a Pacific ciguatoxin (P-CTX-1B) in the neuroblastoma cell assay and the receptor binding assay. Rosmarinic acid and six derivatives were also evaluated by means of these bioassays. For this purpose, we have developed an improved synthetic route for caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE). Results Both the aqueous extract of H. foertherianum leaves and rosmarinic acid showed inhibitory activities against a Pacific ciguatoxin in the above bioassays. Among all the molecules that were evaluated, rosmarinic acid was the most active compound. Conclusion These results confirm further the potential of H. foertherianum in the treatment of Ciguatera Fish Poisoning.
Dominique Laurent - One of the best experts on this subject based on the ideXlab platform.
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protective effect of heliotropium foertherianum boraginaceae folk remedy and its active compound rosmarinic acid against a pacific ciguatoxin
Journal of Ethnopharmacology, 2012Co-Authors: Fanny Rossi, Mireille Chinain, Valerie Jullian, Ralph Pawlowiez, Shilpa Kumarroine, Mohamed Haddad, Taiana H Darius, Nabila Gaertnermazouni, Dominique LaurentAbstract:Abstract Ethnopharmacological relevance Senescent leaves of Heliotropium foertherianum Diane & Hilger (Boraginaceae) are traditionally used in the Pacific region to treat Ciguatera Fish Poisoning. This plant contains rosmarinic acid that is known for its multiple biological activities. In the present study, H. foertherianum aqueous extract, rosmarinic acid and its derivatives were evaluated for their capacity to reduce the effect of ciguatoxins. Materials and methods Aqueous extract of H. foertherianum leaves was prepared and studied for its effects against a Pacific ciguatoxin (P-CTX-1B) in the neuroblastoma cell assay and the receptor binding assay. Rosmarinic acid and six derivatives were also evaluated by means of these bioassays. For this purpose, we have developed an improved synthetic route for caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE). Results Both the aqueous extract of H. foertherianum leaves and rosmarinic acid showed inhibitory activities against a Pacific ciguatoxin in the above bioassays. Among all the molecules that were evaluated, rosmarinic acid was the most active compound. Conclusion These results confirm further the potential of H. foertherianum in the treatment of Ciguatera Fish Poisoning.
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La Ciguatera : de l'étiologie du phénomène au traitement de ses symptômes
EDP Sciences, 2008Co-Authors: Raphaële Boydron-le Garrec, Evelyne Benoit, Martin-pierre Sauviat, Maryvonne Frostin, Dominique LaurentAbstract:La Ciguatera est l'intoxication alimentaire par produits marins la plus commune dans les régions tropicales et subtropicales. De nombreux travaux concernant son étiologie, son épidémiologie et ses manifestations cliniques, mais aussi la découverte des toxines responsables, la mise en évidence de leur transfert, l'étude de leur structure ainsi que l'analyse de leurs effets pharmacologiques ont permis une meilleure compréhension du phénomène ciguatérique. C'est une algue microscopique, un dinoflagellé benthique du genre Gambierdiscus (principalement G. toxicus) qui est à l'origine de la Ciguatera. Dans certaines conditions, cette microalgue produit des toxines, les “ gambiertoxines ”, qui sont les précurseurs d'autres toxines, les ciguatoxines. Les facteurs favorisant cette production sont cependant encore mal connus. L'implication d'autres dinoflagellés, cyanophytes ou bactéries, a été suspectée. Les espèces pisciaires incriminées dans la transmission de la Ciguatera sont bien identifiées dans leur ensemble. Cependant, les toxines présentent des différences d'un océan à l'autre. Les symptômes de l'intoxication, maintenant bien décrits, incluent principalement des troubles digestifs, neurologiques et cardio-vasculaires dont la prépondérance varie selon la nature des toxines impliquées. L'intoxication ciguatérique tend à s'exporter vers des zones non endémiques où elle est encore mal diagnostiquée. Aucun antidote spécifique n'existe à ce jour, et ce n'est que par des traitements symptomatiques ou palliatifs que la Ciguatera est actuellement prise en charge
Mélanie Roué - One of the best experts on this subject based on the ideXlab platform.
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Assessment of Ciguatera and other phycotoxin-related risks in Anaho Bay (Nuku Hiva Island, French Polynesia) : molecular, toxicological, and chemical analyses of passive samplers
Toxins, 2020Co-Authors: Mélanie Roué, Jérôme Viallon, Manoella Sibat, K.f. Smith, K. Henry, A. Ung, L. Biessy, P. Hess, H.t. Darius, Mireille ChinainAbstract:Ciguatera poisoning is a foodborne illness caused by the consumption of seafood contaminated with ciguatoxins (CTXs) produced by dinoflagellates from the genera Gambierdiscus and Fukuyoa. The suitability of Solid Phase Adsorption Toxin Tracking (SPATT) technology for the monitoring of dissolved CTXs in the marine environment has recently been demonstrated. To refine the use of this passive monitoring tool in ciguateric areas, the effects of deployment time and sampler format on the adsorption of CTXs by HP20 resin were assessed in Anaho Bay (Nuku Hiva Island, French Polynesia), a well-known Ciguatera hotspot. Toxicity data assessed by means of the mouse neuroblastoma cell-based assay (CBA-N2a) showed that a 24 h deployment of 2.5 g of resin allowed concentrating quantifiable amounts of CTXs on SPATT samplers. The CTX levels varied with increasing deployment time, resin load, and surface area. In addition to CTXs, okadaic acid (OA) and dinophysistoxin-1 (DTX1) were also detected in SPATT extracts using liquid chromatographycoupled to tandem mass spectrometry (LC-MS/MS), consistent with the presence of Gambierdiscus and Prorocentrum species in the environment, as assessed by quantitative polymerase chain reaction (qPCR) and high-throughput sequencing (HTS) metabarcoding analyses conducted on passive window screen (WS) artificial substrate samples. Although these preliminary findings await further confirmation in follow-up studies, they highlight the usefulness of SPATT samplers in the routine surveillance of CPrisk on a temporal scale, and the monitoring of other phycotoxin-related risks in Ciguatera-prone areas.
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tissue distribution and elimination of ciguatoxins in tridacna maxima tridacnidae bivalvia fed gambierdiscus polynesiensis
Toxins, 2018Co-Authors: Mélanie Roué, Hélène Taiana Darius, André Ung, Jérôme Viallon, Manoella Sibat, Zouher Amzil, Philipp Hess, Mireille ChinainAbstract:Ciguatera is a foodborne disease caused by the consumption of seafood contaminated with ciguatoxins (CTXs). Ciguatera-like poisoning events involving giant clams (Tridacna maxima) are reported occasionally from Pacific islands communities. The present study aimed at providing insights into CTXs tissue distribution and detoxification rate in giant clams exposed to toxic cells of Gambierdiscus polynesiensis, in the framework of seafood safety assessment. In a first experiment, three groups of tissue (viscera, flesh and mantle) were dissected from exposed individuals, and analyzed for their toxicity using the neuroblastoma cell-based assay (CBA-N2a) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) analyses. The viscera, flesh, and mantle were shown to retain 65%, 25%, and 10% of the total toxin burden, respectively. All tissues reached levels above the safety limit recommended for human consumption, suggesting that evisceration alone, a practice widely used among local populations, is not enough to ensure seafood safety. In a second experiment, the toxin content in contaminated giant clams was followed at different time points (0, 2, 4, and 6 days post-exposure). Observations suggest that no toxin elimination is visible in T. maxima throughout 6 days of detoxification.
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Toxicological Investigations on the Sea Urchin Tripneustes gratilla (Toxopneustidae, Echinoid) from Anaho Bay (Nuku Hiva, French Polynesia): Evidence for the Presence of Pacific Ciguatoxins.
Marine drugs, 2018Co-Authors: Hélène Taiana Darius, Patricia A. Tester, R. Wayne Litaker, Mark W. Vandersea, Mélanie Roué, Jérôme Viallon, Manoella Sibat, Zouher Amzil, Clémence Gatti, Philipp HessAbstract:The sea urchin Tripneustes gratilla (Toxopneustidae, Echinoids) is a source of protein for many islanders in the Indo-West Pacific. It was previously reported to occasionally cause Ciguatera-like poisoning; however, the exact nature of the causative agent was not confirmed. In April and July 2015, Ciguatera poisonings were reported following the consumption of T. gratilla in Anaho Bay (Nuku Hiva Island, Marquesas archipelago, French Polynesia). Patient symptomatology was recorded and sea urchin samples were collected from Anaho Bay in July 2015 and November 2016. Toxicity analysis using the neuroblastoma cell–based assay (CBA-N2a) detected the presence of ciguatoxins (CTXs) in T. gratilla samples. Gambierdiscus species were predominant in the benthic assemblages of Anaho Bay, and G. polynesiensis was highly prevalent in in vitro cultures according to qPCR results. Liquid chromatography–tandem mass spectrometry (LC-MS/MS) analyses revealed that P-CTX-3B was the major ciguatoxin congener in toxic sea urchin samples, followed by 51-OH-P-CTX-3C, P-CTX-3C, P-CTX-4A, and P-CTX-4B. Between July 2015 and November 2016, the toxin content in T. gratilla decreased, but was consistently above the safety limit allowed for human consumption. This study provides evidence of CTX bioaccumulation in T. gratilla as a cause of Ciguatera-like poisoning associated with a documented symptomatology.
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Tectus niloticus (Tegulidae, Gastropod) as a Novel Vector of Ciguatera Poisoning: Clinical Characterization and Follow-Up of a Mass Poisoning Event in Nuku Hiva Island (French Polynesia)
MDPI AG, 2018Co-Authors: Clemence Mahana Iti Gatti, Mélanie Roué, Hélène Taiana Darius, Davide Lonati, Arturo Zancan, Azzurra Schicchi, Carlo Alessandro Locatelli, Mireille ChinainAbstract:Ciguatera fish poisoning (CFP) is the most prevalent non-bacterial food-borne form of poisoning in French Polynesia, which results from the consumption of coral reef fish naturally contaminated with ciguatoxins produced by dinoflagellates in the genus Gambierdiscus. Since the early 2000s, this French territory has also witnessed the emergence of atypical forms of Ciguatera, known as Ciguatera shellfish poisoning (CSP), associated with the consumption of marine invertebrates. In June 2014, nine tourists simultaneously developed a major and persistent poisoning syndrome following the consumption of the gastropod Tectus niloticus collected in Anaho, a secluded bay of Nuku Hiva Island (Marquesas Archipelago, French Polynesia). The unusual nature and severity of this event prompted a multidisciplinary investigation in order to characterize the etiology and document the short/long-term health consequences of this mass-poisoning event. This paper presents the results of clinical investigations based on hospital medical records, medical follow-up conducted six and 20 months post-poisoning, including a case description. This study is the first to describe the medical signature of T. niloticus poisoning in French Polynesia and contributed to alerting local authorities about the potential health hazards associated with the consumption of this gastropod, which is highly prized by local communities in Pacific island countries and territories
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Evidence of the bioaccumulation of ciguatoxins in giant clams (Tridacna maxima) exposed to Gambierdiscus spp. cells
Harmful Algae, 2016Co-Authors: Mélanie Roué, Hélène Taiana Darius, Sandy Picot, André Ung, Jérôme Viallon, Nabila Gaertner-mazouni, Manoella Sibat, Zouher Amzil, Mireille ChinainAbstract:Ciguatera Fish Poisoning (CFP) is a foodborne disease classically related to the consumption of tropical coral reef fishes contaminated with ciguatoxins (CTXs), neurotoxins produced by dinoflagellates of the Gambierdiscus genus. Severe atypical Ciguatera-like incidents involving giant,clams, a marine resource highly consumed in the South Pacific, are also frequently reported in many Pacific Islands Countries and Territories. The present study was designed to assess the ability of giant clams to accumulate CTXs in their tissues and highlight the potential health risks associated with their consumption. Since giant clams are likely to be exposed to both free-swimming Gambierdiscus cells and dissolved CTXs in natural environment, ex situ contamination experiments were conducted as follows: giant clams were exposed to live or lyzed cells of TB92, a highly toxic strain of G. polynesiensis containing 5.83 +/- 0.85 pg P-CTX-3C equiv. cell(-1) vs. HIT0, a weakly toxic strain of G. toxicus containing only (2.05 +/- 1.16) x 10(-3) pg P-CTX-3C equiv. cell-1, administered over a 48 h period at a concentration of 150 cells mL(-1). The presence of CTXs in giant clams tissues was further assessed using the mouse neuroblastoma cell-based assay (CBA-N2a). Results showed that giant clams exposed to either lyzed or live cells of TB92 were able to bioaccumulate CTXs at concentrations well above the safety limit recommended for human consumption, i.e. 3.28 +/- 137 and 2.92 +/- 1.03 ng P-CTX-3C equiv. g(-1) flesh (wet weight), respectively, which represented approximately 3% of the total toxin load administered to the animals. In contrast, giant clams exposed to live or lyzed cells of HIT0 were found to be free of toxins, suggesting that in the nature, the risk of contamination of these bivalves is established only in the presence of highly toxic blooms of Gambierdiscus. Liquid chromatography-mass spectrometry (LC-MS/MS) analyses confirmed CBA-N2a results and also revealed that P-CTX-3B was the major CTX congener retained in the tissues of giant clams fed with TB92 cells. To the best of our knowledge, this study is the first to provide evidence of the bioaccumulation of Gambierdiscus CTX.s in giant clams and confirms that these bivalve molluscs can actually constitute another pathway in Ciguatera poisonings. While most monitoring programs currently focus on fish toxicity, these findings stress the importance of a concomitant surveillance of these marine invertebrates in applicable locations for an accurate assessment of Ciguatera risk.
Evelyne Benoit - One of the best experts on this subject based on the ideXlab platform.
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Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells
PLOS ONE, 2008Co-Authors: Daniel G. Baden, Richard J. Lewis, Andrea J. Bourdelais, Peter J. Wen, Truong D. Nguyen-huu, Martha Alvarez, Evelyne Benoit, Frédéric A. Meunier, César Mattei, Jordi MolgóAbstract:Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for Ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of Ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with Ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and β-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for Ciguatera.
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Brevenal inhibits pacific ciguatoxin-1B-induced neurosecretion from bovine chromaffin cells
2008Co-Authors: Peter J. Wen, Daniel G. Baden, Richard J. Lewis, Truong D. Nguyen-huu, Martha Alvarez, Evelyne Benoit, Andrea J, Frédéric A. MeunierAbstract:Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for Ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of Ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with Ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and b-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment fo
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La Ciguatera : de l'étiologie du phénomène au traitement de ses symptômes
EDP Sciences, 2008Co-Authors: Raphaële Boydron-le Garrec, Evelyne Benoit, Martin-pierre Sauviat, Maryvonne Frostin, Dominique LaurentAbstract:La Ciguatera est l'intoxication alimentaire par produits marins la plus commune dans les régions tropicales et subtropicales. De nombreux travaux concernant son étiologie, son épidémiologie et ses manifestations cliniques, mais aussi la découverte des toxines responsables, la mise en évidence de leur transfert, l'étude de leur structure ainsi que l'analyse de leurs effets pharmacologiques ont permis une meilleure compréhension du phénomène ciguatérique. C'est une algue microscopique, un dinoflagellé benthique du genre Gambierdiscus (principalement G. toxicus) qui est à l'origine de la Ciguatera. Dans certaines conditions, cette microalgue produit des toxines, les “ gambiertoxines ”, qui sont les précurseurs d'autres toxines, les ciguatoxines. Les facteurs favorisant cette production sont cependant encore mal connus. L'implication d'autres dinoflagellés, cyanophytes ou bactéries, a été suspectée. Les espèces pisciaires incriminées dans la transmission de la Ciguatera sont bien identifiées dans leur ensemble. Cependant, les toxines présentent des différences d'un océan à l'autre. Les symptômes de l'intoxication, maintenant bien décrits, incluent principalement des troubles digestifs, neurologiques et cardio-vasculaires dont la prépondérance varie selon la nature des toxines impliquées. L'intoxication ciguatérique tend à s'exporter vers des zones non endémiques où elle est encore mal diagnostiquée. Aucun antidote spécifique n'existe à ce jour, et ce n'est que par des traitements symptomatiques ou palliatifs que la Ciguatera est actuellement prise en charge
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nodal swelling produced by ciguatoxin induced selective activation of sodium channels in myelinated nerve fibers
Neuroscience, 1996Co-Authors: Evelyne Benoit, P Juzans, Annemarie Legrand, Jordi MolgóAbstract:Ciguatoxin-1b, the major toxin involved in Ciguatera fish poisoning, and D-mannitol were examined on frog nodes of Ranvier using confocal laser scanning microscopy and conventional current- and voltage-clamp techniques. During the action of 10 nM ciguatoxin-1b, an increase in nodal volume was observed as determined by digital image processing and three-dimensional reconstruction of axons. The increase was prevented by blocking Na+ channels with tetrodotoxin. Ciguatoxin-1b (10 nM) induced high frequency action potential discharges up to 70-100 Hz. Analysis of Na+ current revealed that the toxin modified a current fraction which was activated at resting membrane potential and failed to inactivate. Increasing the osmolality of the external solution by about 50% with D-mannitol restored the nodal volume to its control value and suppressed spontaneous action potentials. In addition, D-mannitol affected unmodified and ciguatoxin-1b-treated Na+ currents in a similar manner causing a reduction of maximum conductance, negative shifts of current reversal potential and modification of the voltage-dependence of current activation and inactivation. In conclusion, ciguatoxin-1b induced a tetrodotoxin-sensitive swelling of nodes of Ranvier and selectively affected the Na+ current of myelinated axons. It is proposed that ciguatoxin-1b, by modifying Na+ current, increased intracellular Na+ concentration which caused water influx and nodal swelling. This may explain some of the reported symptoms of Ciguatera fish poisoning. D-mannitol, an agent used for Ciguatera treatment, was found to reverse the effects of ciguatoxin-1b by reducing Na+ entry and increasing the efflux of water through its osmotic action. It is the first time that osmotic changes produced by the selective activation of ionic channels, i.e. Na+ channels, are reported.
Jordi Molgó - One of the best experts on this subject based on the ideXlab platform.
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Ciguatoxin-induced catecholamine secretion in bovine chromaffin cells: Mechanism of action and reversible inhibition by brevenal.
Toxicon, 2009Co-Authors: Truong D. Nguyen-huu, Daniel G. Baden, Richard J. Lewis, Andrea J. Bourdelais, Peter J. Wen, Jordi Molgó, C Mattei, E Benoit, Frédéric A. MeunierAbstract:Ciguatoxin (P-CTX-1B) from the dinoflagellate Gambierdiscus toxicus, belongs to the family of polyether neurotoxins responsible for the neurological poisoning disorder Ciguatera. Although it is the most widespread marine-borne disease affecting humans, there is no current FDA-approved treatment available except for symptomatic therapies. In this paper, we report that P-CTX-1B promotes catecholamine secretion from bovine chromaffin cells, an effect that is insensitive to concomitant activation of capacitative Ca(2+) entry. Moreover, we confirm that brevenal, a polyether from the dinoflagellate Karenia brevis, blocks P-CTX-1B-induced catecholamine secretion. This effect is partially reversible. Our results therefore raise the prospect of finding functional antagonists for P-CTX-1B that could be useful for the treatment of Ciguatera.
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Brevenal Inhibits Pacific Ciguatoxin-1B-Induced Neurosecretion from Bovine Chromaffin Cells
PLOS ONE, 2008Co-Authors: Daniel G. Baden, Richard J. Lewis, Andrea J. Bourdelais, Peter J. Wen, Truong D. Nguyen-huu, Martha Alvarez, Evelyne Benoit, Frédéric A. Meunier, César Mattei, Jordi MolgóAbstract:Ciguatoxins and brevetoxins are neurotoxic cyclic polyether compounds produced by dinoflagellates, which are responsible for Ciguatera and neurotoxic shellfish poisoning (NSP) respectively. Recently, brevenal, a natural compound was found to specifically inhibit brevetoxin action and to have a beneficial effect in NSP. Considering that brevetoxin and ciguatoxin specifically activate voltage-sensitive Na+ channels through the same binding site, brevenal has therefore a good potential for the treatment of Ciguatera. Pacific ciguatoxin-1B (P-CTX-1B) activates voltage-sensitive Na+ channels and promotes an increase in neurotransmitter release believed to underpin the symptoms associated with Ciguatera. However, the mechanism through which slow Na+ influx promotes neurosecretion is not fully understood. In the present study, we used chromaffin cells as a model to reconstitute the sequence of events culminating in ciguatoxin-evoked neurosecretion. We show that P-CTX-1B induces a tetrodotoxin-sensitive rise in intracellular Na+, closely followed by an increase in cytosolic Ca2+ responsible for promoting SNARE-dependent catecholamine secretion. Our results reveal that brevenal and β-naphtoyl-brevetoxin prevent P-CTX-1B secretagogue activity without affecting nicotine or barium-induced catecholamine secretion. Brevenal is therefore a potent inhibitor of ciguatoxin-induced neurotoxic effect and a potential treatment for Ciguatera.
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nodal swelling produced by ciguatoxin induced selective activation of sodium channels in myelinated nerve fibers
Neuroscience, 1996Co-Authors: Evelyne Benoit, P Juzans, Annemarie Legrand, Jordi MolgóAbstract:Ciguatoxin-1b, the major toxin involved in Ciguatera fish poisoning, and D-mannitol were examined on frog nodes of Ranvier using confocal laser scanning microscopy and conventional current- and voltage-clamp techniques. During the action of 10 nM ciguatoxin-1b, an increase in nodal volume was observed as determined by digital image processing and three-dimensional reconstruction of axons. The increase was prevented by blocking Na+ channels with tetrodotoxin. Ciguatoxin-1b (10 nM) induced high frequency action potential discharges up to 70-100 Hz. Analysis of Na+ current revealed that the toxin modified a current fraction which was activated at resting membrane potential and failed to inactivate. Increasing the osmolality of the external solution by about 50% with D-mannitol restored the nodal volume to its control value and suppressed spontaneous action potentials. In addition, D-mannitol affected unmodified and ciguatoxin-1b-treated Na+ currents in a similar manner causing a reduction of maximum conductance, negative shifts of current reversal potential and modification of the voltage-dependence of current activation and inactivation. In conclusion, ciguatoxin-1b induced a tetrodotoxin-sensitive swelling of nodes of Ranvier and selectively affected the Na+ current of myelinated axons. It is proposed that ciguatoxin-1b, by modifying Na+ current, increased intracellular Na+ concentration which caused water influx and nodal swelling. This may explain some of the reported symptoms of Ciguatera fish poisoning. D-mannitol, an agent used for Ciguatera treatment, was found to reverse the effects of ciguatoxin-1b by reducing Na+ entry and increasing the efflux of water through its osmotic action. It is the first time that osmotic changes produced by the selective activation of ionic channels, i.e. Na+ channels, are reported.