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COMPARISON OF THE IN VIVO AND IN VITRO ACUTE TOXICITY OF PALYTOXIN

Andrea Boente-Juncal1, Carmen Vale1, Mercedes Camiña2, Mercedes Vieytes2, Manuel Cifuentes3, Amparo Alfonso1 and Luis M. Botana1*
  • 1 Departamento Farmacología,Farmacia y Tecnología Farmacéutica. Facultad Veterinaria Lugo, Universidad Santiago de Compostela, Spain
  • 2 Departamento de Fisiología, Facultad de Veterinaria, Universidad de Santiago de Compostela, Spain
  • 3 Departamento de Anatomía y Anatomía Patológica Comparadas, Facultad de Veterinaria,Universidad de Santiago de Compostela, Spain

Palytoxin (PLTX) is one of the most poisonous substances known to date (Moore and Scheuer, 1971). 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. PLTX production is associated to dinoflagelates of the genus Ostreopsis (Patocka et al., 2018). During the last decade, benthonic dinoflagellates of the genus Ostreopsis, that before were usually found in tropical areas, have expanded their distribution to temperate waters and have been reported in some European countries such as France, Germany, Greece, Italy, Cyprus, Spain and Portugal (Silva et al., 2015; Botana, 2016). Therefore, PLTX is considered an emergent marine toxin and a new food security concern in Europe. PLTX binds to the Na+-K+ ATPase transforming it in a non selective ion channel (Artigas and Gadsby, 2003) and causing cell membrane depolarization and disruption of ion homeostasis in eucariotic cells. Although the presence of palytoxin in marine products is currently not regulated in Europe, in 2009, the European Food Safety Authority (EFSA) expressed its opinion on PLTX toxicity (EFSA, 2009) and, from the few available in vivo acute toxicity studies, derived an Acute Reference Dose (ARfD) in humans of 0.2 μg/kg, and a maximum concentration of PLTX and related compounds in shellfish of 30 μg/kg shellfish meat. In this work we have evaluated the acute toxicity of PLTX both by oral (gavage) and intraperitoneal administration to Swiss mice and compared it with the citotoxicity elicited by the toxin in primary cultures of cerebellar granule cells. To determine the oral toxicity Swiss mice were administered PLTX ranging from 36 to 1200 µg/Kg following the up and down procedure recommended by the OECD. For intraperitoneal toxicity PLTX doses ranged from 0.0066 to 3 µg/Kg and, in both cases, mice were observed during 4 days. With these data both the lethal dose 50 (LD50) and the no observed adverse effect level (NOAEL) for PLTX by the oral and intraperitoneal routes were determined and compared with the in vitro toxicity of the compound, following a method previously proposed for the routine determination and monitoring of palytoxins.

Acknowledgements

The research has received funding from the following FEDER cofounded-grants. From CDTI and Technological Funds, supported by Ministerio de Economía, Industria y Competitividad, AGL2014-58210-R, AGL2016-78728-R (AEI/FEDER, UE), ISCIII/PI16/01830 and RTC-2016-5507-2. From CDTI under ISIP Programme, Spain, IDI-20130304 APTAFOOD and ITC-20161072. From European Union POCTEP 0161-Nanoeaters-1-E-1, and Interreg AlertoxNet EAPA-317-2016. ABJ is recipient a fellows from the Spanish Ministry of Education.

References

Artigas P, Gadsby DC (2003) Na+/K+-pump ligands modulate gating of palytoxin-induced ion channels. Proc Natl Acad Sci U S A 100:501-505.
Botana LM (2016) Toxicological Perspective on Climate Change: Aquatic Toxins. Chem Res Toxicol 29:619-625.
EFSA (2009) EFSA Panel on Contaminants in the Food Chain (CONTAM); Scientific Opinion on marine biotoxins in shellfish–Palytoxin group. EFSA Journal 7:1393. [1338 pp.].
Moore RE, Scheuer PJ (1971) Palytoxin: a new marine toxin from a coelenterate. Science 172:495-498.
Patocka J, Nepovimova E, Wu Q, Kuca K (2018) Palytoxin congeners. Archives of Toxicology 92:143-156.
Silva M, Pratheepa VK, Botana LM, Vasconcelos V (2015) Emergent toxins in North Atlantic temperate waters: a challenge for monitoring programs and legislation. Toxins (Basel) 7:859-885.

Keywords: Palytoxin, Acute toxicity study, Na+-K+ ATpase, mouse models, oral administration, intraperitoneal administration

Conference: IMMR'18 | International Meeting on Marine Research 2018, Peniche, Portugal, 5 Jul - 6 Jul, 2018.

Presentation Type: Poster Presentation

Topic: Fisheries and Management

Citation: Boente-Juncal A, Vale C, Camiña M, Vieytes M, Cifuentes M, Alfonso A and Botana LM (2019). COMPARISON OF THE IN VIVO AND IN VITRO ACUTE TOXICITY OF PALYTOXIN. Front. Mar. Sci. Conference Abstract: IMMR'18 | International Meeting on Marine Research 2018. doi: 10.3389/conf.FMARS.2018.06.00022

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Received: 28 Apr 2018; Published Online: 07 Jan 2019.

* Correspondence: Prof. Luis M Botana, Departamento Farmacología,Farmacia y Tecnología Farmacéutica. Facultad Veterinaria Lugo, Universidad Santiago de Compostela, Lugo, Spain, luis.botana@usc.es