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The Investigation of Toxic Effects on Palytoxin by Using Cell Model

學生姓名: 吳尚宜
指導教授: 黃登福
學  號: 10432065
學期: 105上
摘  要: Palytoxin (PLTX) is a polyhydroxylated polyether. PLTX is found in zoanthids which are marine organisms from tropical and subtropical areas. PLTX and analogues are considered as the causative agents of human seafood poisoning with symptoms of gastro-intestinal malaise, myalgia, muscular cramps, dyspnea and arrhythmias. The report is divided into three parts for elucidating PLTX toxicity. First, human skin keratinocytes cells was used as cell model to investigate PLTX-induced cytotoxicity. The results indicated that among the chain of intracellular events following the interaction of PLTX with the Na+-K+ ATPase the first and crucial step is the increased intracellular Na+ concentration that triggers a sequence of cell dysfunction, leading to an irreversible cell death. In addition, the differentiated Caco-2 cell monolayers were used to investigate the passage of PLTX through the human intestinal barrier by employing a well-characterized and accepted in vitro model of intestinal permeability. Permeability assays showed that PLTX could not significantly pass the Caco-2 monolayer, despite the lack of epithelium integrity, suggesting that PLTX would be poorly transported to blood, which may explain its lower oral toxicity. At last, the in vivo and in vitro effects of 42-OH-PLTX on skeletal muscle, one of the most sensitive targets for PLTX, were investigate. The results demonstrated that 42-OH-PLTX caused 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.
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