OBJECTIVES Clinically approved iron chelators are effective in decreasing significant transfusional iron accumulation. Starch-Deferoxamine (S-DFO), a novel high molecular weight iron chelator, was produced to increase binding capacity to iron and reduce toxicity. Although its efficacy was established in one small cohort clinical trial, its potential adverse effect was not adequately addressed. METHODS We utilized zebrafish model to assess S-DFO toxicity using following assays: mortality, teratogenicity, hatching rate, tail flicking, Acridine Orange staining for apoptosis detection, o-dianisidine staining for hemoglobin synthesis, and the level of Hsp70 as a general stress indicator. Embryos were exposed to different concentrations of S-DFO, Zinc Oxide nanoparticle (ZnO) (positive control), along with untreated control (UC). RESULTS S-DFO showed no significant mortality nor deformities at all tested concentrations (0.0-1000 μM). Thus, the LC50 is expected to >1000 μM. 100 μM S-DFO treatment did not affect embryo development (as judged by hatching rate); neuromuscular activity (as judged by tail flicking); and hemoglobin synthesis. Neither apoptosis, nor increase in Hsp70 level was noticed upon S-DFO treatment. CONCLUSION Our assays demonstrate that S-DFO does not induce cellular or biochemical stress and has no adverse effect on organ development of zebrafish embryos, suggesting its safe use as an iron chelator.

中文翻译：

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与氧化锌纳米粒子相比，新型铁螯合剂淀粉-去铁胺（S-DFO）对斑马鱼胚胎的生物相容性和毒性：基于氧化应激的细胞凋亡，理化和神经学研究概况。

目的经临床批准的铁螯合剂可有效减少大量输血铁累积。淀粉-去铁胺（S-DFO）是一种新型的高分子量铁螯合剂，可提高与铁的结合能力并降低毒性。尽管其功效在一项小型队列临床试验中得到证实，但其潜在的不良反应尚未得到充分解决。方法我们使用斑马鱼模型通过以下测定评估S-DFO毒性：死亡率，致畸性，孵化率，甩尾，A啶橙染色用于细胞凋亡检测，邻联二苯胺染色用于血红蛋白合成，以及Hsp70水平作为一般应激指标。胚胎暴露于不同浓度的S-DFO，氧化锌纳米颗粒（ZnO）（阳性对照）以及未经处理的对照（UC）。结果在所有测试浓度（0.0-1000μM）下，S-DFO均未显示出明显的死亡率或畸形。因此，预期LC50> 1000μM。100μMS-DFO处理不影响胚胎发育（根据孵化率判断）；神经肌肉活动（通过甩尾判断）；和血红蛋白合成。S-DFO处理后未发现凋亡或Hsp70水平升高。结论我们的测定表明，S-DFO不会诱导细胞或生化应激，并且对斑马鱼胚胎的器官发育没有不利影响，表明它可以安全地用作铁螯合剂。神经肌肉活动（通过甩尾判断）；和血红蛋白合成。S-DFO处理后未发现凋亡或Hsp70水平升高。结论我们的测定方法证明S-DFO不会诱导细胞或生化应激，并且对斑马鱼胚胎的器官发育没有不利影响，表明它可以安全地用作铁螯合剂。神经肌肉活动（通过甩尾判断）；和血红蛋白合成。S-DFO处理后未发现凋亡或Hsp70水平升高。结论我们的测定方法证明S-DFO不会诱导细胞或生化应激，并且对斑马鱼胚胎的器官发育没有不利影响，表明它可以安全地用作铁螯合剂。