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The consumption of contaminated shellfish with okadaic acid (OA) group of toxins leads to diarrhoeic shellfish poisoning (DSP) characterized by a set of symptoms including nausea, vomiting and diarrhoea. These phycotoxins are Ser/Thr phosphatase inhibitors, which produce hyperphosphorylation in cellular proteins. However, this inhibition does not fully explain the symptomatology reported and other targets could be relevant to the toxicity. Previous studies have indicated a feasible involvement of the nervous system. We performed a set of in vivo approaches to elucidate whether neuropeptide Y (NPY), Peptide YY (PYY) or serotonin (5-HT) was implicated in the early OA-induced diarrhoea. Fasted Swiss female mice were administered NPY, PYY(3–36) or cyproheptadine intraperitoneal prior to oral OA treatment (250 µg/kg). A non-significant delay in diarrhoea onset was observed for NPY (107 µg/kg) and PYY(3–36) (1 mg/kg) pre-treatment. On the contrary, the serotonin antagonist cyproheptadine was able to block (10 mg/kg) or delay (0.1 and 1 mg/kg) diarrhoea onset suggesting a role of 5-HT. This is the first report of the possible involvement of serotonin in OA-induced poisoning.
M. Carmen Louzao; Celia Costas; Paula Abal; Toshiyuki Suzuki; Ryuichi Watanabe; Natalia Vilariño; Cristina Carrera; Andrea Boente-Juncal; Carmen Vale; Mercedes R. Vieytes; Luis M. Botana. Serotonin involvement in okadaic acid-induced diarrhoea in vivo. Archives of Toxicology 2021, 95, 1 -17.
AMA StyleM. Carmen Louzao, Celia Costas, Paula Abal, Toshiyuki Suzuki, Ryuichi Watanabe, Natalia Vilariño, Cristina Carrera, Andrea Boente-Juncal, Carmen Vale, Mercedes R. Vieytes, Luis M. Botana. Serotonin involvement in okadaic acid-induced diarrhoea in vivo. Archives of Toxicology. 2021; 95 (8):1-17.
Chicago/Turabian StyleM. Carmen Louzao; Celia Costas; Paula Abal; Toshiyuki Suzuki; Ryuichi Watanabe; Natalia Vilariño; Cristina Carrera; Andrea Boente-Juncal; Carmen Vale; Mercedes R. Vieytes; Luis M. Botana. 2021. "Serotonin involvement in okadaic acid-induced diarrhoea in vivo." Archives of Toxicology 95, no. 8: 1-17.
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.
Paz Otero; Carmen Vale; Andrea Boente-Juncal; Celia Costas; M. Louzao; Luis Botana. Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis. Toxins 2020, 12, 613 .
AMA StylePaz Otero, Carmen Vale, Andrea Boente-Juncal, Celia Costas, M. Louzao, Luis Botana. Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis. Toxins. 2020; 12 (10):613.
Chicago/Turabian StylePaz Otero; Carmen Vale; Andrea Boente-Juncal; Celia Costas; M. Louzao; Luis Botana. 2020. "Detection of Cyclic Imine Toxins in Dietary Supplements of Green Lipped Mussels (Perna canaliculus) and in Shellfish Mytilus chilensis." Toxins 12, no. 10: 613.
Palytoxin (PLTX) is one of the most poisonous substances known to date and considered as an emergent toxin in Europe. Palytoxin binds to the Na+-K+ ATPase, converting the enzyme in a permeant cation channel. This toxin is known for causing human fatal intoxications associated with the consumption of contaminated fish and crustaceans such as crabs, groupers, mackerel, and parrotfish. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Different reports have previously explored the acute oral toxicity of PLTX in mice. Although the presence of palytoxin in marine products is currently not regulated in Europe, the European Food Safety Authority expressed its opinion on PLTX and demanded assessment for chronic toxicity studies of this potent marine toxin. In this study, the chronic toxicity of palytoxin was evaluated after oral administration to mice by gavage during a 28-day period. After chronic exposure of mice to the toxin, a lethal dose 50 (LD50) of 0.44 µg/kg of PLTX and a No-Observed-Adverse-Effect Level (NOAEL) of 0.03 µg/kg for repeated daily oral administration of PLTX were determined. These results indicate a much higher chronic toxicity of PLTX and a lower NOAEL than that previously described in shorter treatment periods, pointing out the need to further reevaluate the levels of this compound in marine products.
Andrea Boente-Juncal; Sandra Raposo-García; Carmen Vale; M. Carmen Louzao; Paz Otero; Luis M. Botana. In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin. Toxins 2020, 12, 489 .
AMA StyleAndrea Boente-Juncal, Sandra Raposo-García, Carmen Vale, M. Carmen Louzao, Paz Otero, Luis M. Botana. In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin. Toxins. 2020; 12 (8):489.
Chicago/Turabian StyleAndrea Boente-Juncal; Sandra Raposo-García; Carmen Vale; M. Carmen Louzao; Paz Otero; Luis M. Botana. 2020. "In Vivo Evaluation of the Chronic Oral Toxicity of the Marine Toxin Palytoxin." Toxins 12, no. 8: 489.
Tetrodotoxin (TTX) is a potent natural toxin causative of human food intoxications that shares its mechanism of action with the paralytic shellfish toxin saxitoxin (STX). Both toxins act as potent blockers of voltage-gated sodium channels. Although human intoxications by TTX were initially described in Japan, nowadays increasing concern about the regulation of this toxin in Europe has emerged due to its detection in fish and mollusks captured in European waters. Currently, TTX is only regularly monitored in Dutch fishery products. However, the European Food Safety Authority (EFSA) has established a safety level of 44 µg/kg TTX as the amount of toxin that did not cause adverse effects in humans. This level was extrapolated considering initial data on its acute oral toxicity and EFSA remarked the need for chronic toxicity studies to further reduce the uncertainty of future toxin regulations. Thus, in this work, we evaluated the oral chronic toxicity of TTX using the safety levels initially recommended by EFSA in order to exclude potential human health risks associated with the worldwide expanding presence of TTX. Using internationally recommended guidelines for the assessment of oral chronic toxicity, the data provided here support the proposed safety level for TTX as low enough to prevent human adverse effects of TTX even after chronic daily exposure to the toxin. However, the combination of TTX with STX at doses above the maximal exposure level of 5.3 µg/kg body weight derived by EFSA increased the lethality of TTX, thus confirming that both TTX and paralytic shellfish toxins should be taken into account to assess human health risks.
Andrea Boente-Juncal; Paz Otero; Inés Rodríguez; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Carmen Vale; Luis M. Botana. Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin. Toxins 2020, 12, 312 .
AMA StyleAndrea Boente-Juncal, Paz Otero, Inés Rodríguez, Mercedes Camiña, Mercedes Rodriguez-Vieytes, Carmen Vale, Luis M. Botana. Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin. Toxins. 2020; 12 (5):312.
Chicago/Turabian StyleAndrea Boente-Juncal; Paz Otero; Inés Rodríguez; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Carmen Vale; Luis M. Botana. 2020. "Oral Chronic Toxicity of the Safe Tetrodotoxin Dose Proposed by the European Food Safety Authority and Its Additive Effect with Saxitoxin." Toxins 12, no. 5: 312.
Palytoxin is an emergent toxin in Europe and one of the most toxic substances know to date. The toxin disrupts the physiological functioning of the Na+/K+-ATPase converting the enzyme in a permeant cation channel. Human intoxications by PLTX after consumption of contaminated fishery products are a serious health issue and can be fatal. Several reports have previously investigated the oral and intraperitoneal toxicity of PLTX in mice. However, in all cases short observation periods (24 and 48 h) after toxin administration were evaluated. In this work, single oral or intraperitoneal doses of PLTX were administered to healthy mice and surviving animals were followed up for 96 h. The data obtained here allowed us to calculate the oral and intraperitoneal lethal doses 50 (LD50) which were in the range of the values previously described. Surprisingly, the oral NOAEL for PLTX was more than 10 times lower than that previously described, a fact that indicates the need for the reevaluation of the levels of the toxin in edible fishery products.
Andrea Boente-Juncal; Carmen Vale; Mercedes Camiña; J. Manuel Cifuentes; Mercedes R. Vieytes; Luis M. Botana. Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL). Toxicon 2020, 177, 16 -24.
AMA StyleAndrea Boente-Juncal, Carmen Vale, Mercedes Camiña, J. Manuel Cifuentes, Mercedes R. Vieytes, Luis M. Botana. Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL). Toxicon. 2020; 177 ():16-24.
Chicago/Turabian StyleAndrea Boente-Juncal; Carmen Vale; Mercedes Camiña; J. Manuel Cifuentes; Mercedes R. Vieytes; Luis M. Botana. 2020. "Reevaluation of the acute toxicity of palytoxin in mice: Determination of lethal dose 50 (LD50) and No-observed-adverse-effect level (NOAEL)." Toxicon 177, no. : 16-24.
Tetrodotoxin (TTX) is one of the most potent naturally occurring neurotoxins. InitiallyTTX was associated with human food intoxications in Japan, but nowadays, concerns about thehuman health risks posed by TTX have increased in Europe after the identification of the toxin infish, marine gastropods, and bivalves captured in European waters. Even when TTX monitoring isnot currently performed in Europe, an acute oral no observable effect level (NOAEL) of 75 μg/kghas been recently established but, to date, no studies evaluating the chronic oral toxicity of TTXhave been released, even when EFSA has highlighted the need for them. Thus, in this work, thechronic effects of low oral TTX doses (below the acute lethal dose 50) were evaluated followinginternationally adopted guidelines. The results presented here demonstrate that low oral doses ofTTX have deleterious effects on renal and cardiac tissues. Moreover, alterations in bloodbiochemistry parameters, urine production, and urinalysis data were already detected at the oraldose of 75 μg/kg after the 28 days exposure. Thus, the data presented here constitute an initialapproach for the chronic evaluation of the in vivo toxicity of tetrodotoxin after its ingestion throughcontaminated fishery products.
Andrea Boente-Juncal; Carmen Vale; Manuel Cifuentes; Paz Otero; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Luis Miguel Botana. Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity. Toxins 2019, 11, 96 .
AMA StyleAndrea Boente-Juncal, Carmen Vale, Manuel Cifuentes, Paz Otero, Mercedes Camiña, Mercedes Rodriguez-Vieytes, Luis Miguel Botana. Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity. Toxins. 2019; 11 (2):96.
Chicago/Turabian StyleAndrea Boente-Juncal; Carmen Vale; Manuel Cifuentes; Paz Otero; Mercedes Camiña; Mercedes Rodriguez-Vieytes; Luis Miguel Botana. 2019. "Chronic In Vivo Effects of Repeated Exposure to Low Oral Doses of Tetrodotoxin: Preliminary Evidence of Nephrotoxicity and Cardiotoxicity." Toxins 11, no. 2: 96.
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.
Andrea Boente-Juncal; Mercedes Álvarez; Álvaro Antelo; Inés Rodríguez; Kevin Calabro; Carmen Vale; Olivier P. Thomas; Luis M. Botana. Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus. Toxins 2019, 11, 79 .
AMA StyleAndrea Boente-Juncal, Mercedes Álvarez, Álvaro Antelo, Inés Rodríguez, Kevin Calabro, Carmen Vale, Olivier P. Thomas, Luis M. Botana. Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus. Toxins. 2019; 11 (2):79.
Chicago/Turabian StyleAndrea Boente-Juncal; Mercedes Álvarez; Álvaro Antelo; Inés Rodríguez; Kevin Calabro; Carmen Vale; Olivier P. Thomas; Luis M. Botana. 2019. "Structure Elucidation and Biological Evaluation of Maitotoxin-3, a Homologue of Gambierone, from Gambierdiscus belizeanus." Toxins 11, no. 2: 79.