In vivo and in vitro effects of 42-hydroxy-palytoxin on mouse skeletal muscle: structural and functional impairment

tPalytoxins (PLTXs) are known seafood contaminants and their entrance into the food chain raises concernabout possible effects on human health. The increasing number of analogs being identified in ediblemarine 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 toxicityrepresents an important step toward a better comprehension of the mechanism of action of this family ofcompounds. From this perspective, the aim of this work was to investigate the in vivo and in vitro effectof 42-OH-PLTX on skeletal muscle, one of the most sensitive targets for PLTXs. Our results demonstratethat 42-OH-PLTX causes damage at the skeletal muscle level with a cytotoxic potency similar to thatof PLTX. 42-OH-PLTX induces cytotoxicity and cell swelling in a Na+-dependent manner similar to theparent compound. However, the limited Ca2+-dependence of the toxic insult induced by 42-OH-PLTXsuggests a specific mechanism of action for this analog. Our results also suggest an impaired response tothe physiological agonist acetylcholine and altered cell elasticity.