title: Toxicity of palytoxin after repeated oral exposure in mice and in vitro effects on cardiomyocytes.
abstract: Palytoxin (PLTX) is a highly toxic hydrophilic polyether detected in several edible marine organisms from intra-tropical areas, where seafood poisoning were reported. Symptoms usually start with gastro-intestinal malaise, often accompanied by myalgia, muscular cramps, dyspnea and, sometimes, arrhythmias. Monitoring programs in the Mediterranean Sea have detected PLTX-like molecules in edible mollusks and echinoderms. Despite the potential exposure of the human population and its high toxic potential, the toxicological profile of the molecule is still an issue. Thus, the effects of repeated oral administration of PLTX in mice were investigated. Seven days of PLTX administration caused lethality and toxic effects at doses ≥ 30 μg/kg/day. A NOAEL was estimated equal to 3 μg/kg/day, indicating a quite steep dose-response curve. This value, due to the limited number of animal tested, is provisional, although represents a sound basis for further testing. Macroscopic alterations at gastrointestinal level (gastric ulcers and intestinal fluid accumulation) were observed in mice dead during the treatment period. Histological analysis highlighted severe inflammation, locally associated with necrosis, at pulmonary level, as well as hyper-eosinophilia and fiber separation in myocardium. A cardiac damage was supported by the in vitro effect of the toxin on cardiomyocytes, indicating a severe and irreversible impairment of their electrical properties: electrophysiological recordings detected a progressive cell depolarization, arrest of action potentials and beating.
authors.affiliation: Department of Life Sciences, University of Trieste, 34127 Trieste, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Del Favero
authors.forename: Dario
authors.initials: D
authors.lastname: Beltramo
authors.forename: Marina
authors.initials: M
authors.lastname: Sciancalepore
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzon
authors.forename: Tamara
authors.initials: T
authors.lastname: Coslovich
authors.forename: Mark
authors.initials: M
authors.lastname: Poli
authors.forename: Emanuela
authors.initials: E
authors.lastname: Testai
authors.forename: Silvio
authors.initials: S
authors.lastname: Sosa
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
mesh_terms: D000178:Acrylamides / Q000008:administration & dosage* / Q000633:toxicity*; D000284:Administration, Oral; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D002478:Cells, Cultured; D003064:Cnidarian Venoms; D004305:Dose-Response Relationship, Drug; D005260:Female; D008099:Liver / Q000473:pathology; D008168:Lung / Q000473:pathology; D051379:Mice; D009206:Myocardium / Q000473:pathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D019055:No-Observed-Adverse-Effect Level; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D013154:Spleen / Q000473:pathology; D013270:Stomach / Q000473:pathology; D000095702:Polyether Toxins
chemical_list: D000178:Acrylamides; D003064:Cnidarian Venoms; C010272:palytoxin; D000095702:Polyether Toxins
keywords: Cardiomyocytes; Mice; Oral administration; Palytoxin; Repeated dose toxicity