title: In vivo and in vitro effects of 42-hydroxy-palytoxin on mouse skeletal muscle: structural and functional impairment.
abstract: Palytoxins (PLTXs) are known seafood contaminants and their entrance into the food chain raises concern about possible effects on human health. The increasing number of analogs being identified in edible marine organisms complicates the estimation of the real hazard associated with the presence of PLTX-like compounds. So far, 42-OH-PLTX is one of the few congeners available, and the study of its toxicity represents an important step toward a better comprehension of the mechanism of action of this family of compounds. From this perspective, the aim of this work was to investigate the in vivo and in vitro effect of 42-OH-PLTX on skeletal muscle, one of the most sensitive targets for PLTXs. Our results demonstrate that 42-OH-PLTX causes damage at the skeletal muscle level with a cytotoxic potency similar to that of PLTX. 42-OH-PLTX induces cytotoxicity and cell swelling in a Na(+)-dependent manner similar to the parent compound. However, the limited Ca(2+)-dependence of the toxic insult induced by 42-OH-PLTX suggests a specific mechanism of action for this analog. Our results also suggest an impaired response to the physiological agonist acetylcholine and altered cell elasticity.
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Via A. Valerio 6A, 34127 Trieste, Italy.
authors.forename: Giorgia
authors.initials: G
authors.lastname: Del Favero
authors.affiliation: Department of Life Sciences, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy.
authors.forename: Silvio
authors.initials: S
authors.lastname: Sosa
authors.affiliation: United States Army Medical Research Institute of Infectious Diseases, Fort Detrick, MD 21701-5011, USA.
authors.forename: Mark
authors.initials: M
authors.lastname: Poli
authors.affiliation: Department of Life Sciences, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy. Electronic address: tubaro@units.it.
authors.forename: Aurelia
authors.initials: A
authors.lastname: Tubaro
authors.affiliation: Department of Engineering and Architecture, University of Trieste, Via A. Valerio 6A, 34127 Trieste, Italy.
authors.forename: Orfeo
authors.initials: O
authors.lastname: Sbaizero
authors.affiliation: Department of Life Sciences, University of Trieste, Via A. Fleming 22, 34127 Trieste, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Lorenzon
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D003064:Cnidarian Venoms / Q000633:toxicity*; D005260:Female; D008297:Male; D008387:Marine Toxins / Q000633:toxicity*; D051379:Mice; D008807:Mice, Inbred BALB C; D018625:Microscopy, Atomic Force; D018482:Muscle, Skeletal / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D010078:Oxazines; D011714:Pyrans / Q000633:toxicity*; D012235:Rhodamines; D012964:Sodium / Q000378:metabolism; D014966:Xanthenes; D000095702:Polyether Toxins
chemical_list: D002118:Calcium; D003064:Cnidarian Venoms; D008387:Marine Toxins; D010078:Oxazines; D011714:Pyrans; D012235:Rhodamines; D012964:Sodium; D014966:Xanthenes; C005843:resazurin; C022027:lissamine rhodamine B; C547187:42-hydroxypalytoxin; D000095702:Polyether Toxins
keywords: 42-Hydroxy-palytoxin; Calcium; Cell elasticity; Cytotoxicity; Skeletal muscle