Department of Biochemistry and Molecular Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan; Graduate Institute of Medical Sciences, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Department of Anatomy and Cell Biology, School of Medicine, College of Medicine, Taipei Medical University, Taipei 11031, Taiwan.
Carbohydr Polym. 2020 Jul 15;240:116164. doi: 10.1016/j.carbpol.2020.116164. Epub 2020 Apr 13.
Chitosan is suggested as no or low toxicity and biocompatible biomaterial. Digestion of chitosan to reduce molecular weight and formulate nanoparticle was generally used to improve efficiency for DNA or protein delivery. However, the toxicity of low-molecular-weight chitosan (LMWCS) towards freshwater fishes has not been well evaluated. Here, we reported the toxic mechanism of LMWCS using zebrafish (Danio rerio) liver (ZFL) cell line, zebrafish larvae, and adult fish. LMWCS rapidly induced cytotoxicity of ZFL cells and death of zebrafish. Cell membrane damaged by LMWCS reduced cell viability. Damaged membrane of epithelial cell in zebrafish larvae induced breakage of the yolk. Adult fish exhibited hypoxia before death due to multiple damages induced by LMWCS. Although the toxicity of LMWCS was revealed in zebrafish model, the toxicity was only present in pH < 7 and easy be neutralized by other negative ions. Collectively, these data improved a new understanding of LMWCS properties.
壳聚糖被认为是一种低毒、生物相容性的生物材料。为了提高 DNA 或蛋白质的递送效率,通常将壳聚糖消化以降低分子量并形成纳米颗粒。然而,低分子量壳聚糖(LMWCS)对淡水鱼类的毒性尚未得到很好的评估。在这里,我们使用斑马鱼(Danio rerio)肝脏(ZFL)细胞系、斑马鱼幼虫和成年鱼报告了 LMWCS 的毒性机制。LMWCS 可快速诱导 ZFL 细胞的细胞毒性和斑马鱼的死亡。LMWCS 破坏细胞膜,降低细胞活力。LMWCS 破坏斑马鱼幼虫上皮细胞的细胞膜,导致卵黄破裂。由于 LMWCS 引起的多种损伤,成年鱼在死亡前表现出缺氧。尽管在斑马鱼模型中揭示了 LMWCS 的毒性,但只有在 pH < 7 时才会出现毒性,并且很容易被其他阴离子中和。总的来说,这些数据提高了对 LMWCS 特性的新认识。