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

• The biotoxin 42-hydroxy-palytoxin (42-OH-PLTX) damages skeletal muscle in vivo.
• Like PLTX, 42-OH-PLTX induces Na+-dependent cytotoxicity and cell swelling.
• The limited Ca2+-dependency of the cytotoxicity indicates a specific action.
• Exposure to 42-OH-PLTX impairs cholinergic response and alters cell elasticity.

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 Ca2+-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.

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