Department of Engineering and Architecture, University of Trieste, Via A. Valerio 6A, 34127 Trieste, Italy.
Department of Life Sciences, University of Trieste, Via A. Valerio 6, 34127 Trieste, Italy.
Toxicol Lett. 2014 Mar 3;225(2):285-93. doi: 10.1016/j.toxlet.2013.12.020. Epub 2013 Dec 27.
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.
多甲藻毒素 (PLTXs) 是已知的海鲜污染物，它们进入食物链引起了人们对其可能对人类健康造成影响的关注。在可食用海洋生物中鉴定出的类似物数量不断增加，这使得评估与 PLTX 类似化合物存在相关的实际危害变得更加复杂。到目前为止，42-OH-PLTX 是少数几种可用的同系物之一，对其毒性的研究代表了朝着更好地理解此类化合物作用机制迈出的重要一步。从这个角度来看，这项工作的目的是研究 42-OH-PLTX 对骨骼肌的体内和体外影响，骨骼肌是对 PLTXs 最敏感的靶标之一。我们的结果表明，42-OH-PLTX 会导致骨骼肌损伤，其细胞毒性效力与 PLTX 相似。42-OH-PLTX 以类似于母体化合物的方式诱导细胞肿胀和细胞毒性，这是一种依赖于 Na(+) 的方式。然而，42-OH-PLTX 诱导的毒性损伤对 Ca(2+) 的依赖性有限，这表明该类似物具有特定的作用机制。我们的结果还表明，对生理激动剂乙酰胆碱的反应受损，并且细胞弹性发生改变。
