Abstract：
Exposure to environmental contaminants frequently induces the occurrence of blood diseases, but the underlying molecular mechanisms are scarcely known. The toxicity of Diflovidazin (DFD), a widely used mite-remover, to the blood system of non-target organisms requires urgent elucidation. To investigate the deleterious effects of DFD (2, 2.5, and 3 mg/L) on the development and survive of hematopoietic stem cells (HSCs), the zebrafish model was used in this study. DFD exposure reduced the number of HSCs and their subtypes, including macrophages, neutrophils, thymus T-cells, erythrocytes, and platelets. The significant changes in the abnormal apoptosis and differentiation of HSCs were the major reasons for the reduction in blood cells. Using small-molecule antagonists and p53 morpholino revealed that the NF-κB/p53 pathway was responsible for the apoptosis of HSCs upon DFD exposure. The restoration results attributed to the TLR4 inhibitor and molecular docking showed that the TLR4 protein, which was upstream of NF-κB signaling, played a vital role in DFD toxicology. This study elucidates the role and molecular mechanism of DFD in damaging zebrafish HSCs. It provides a theoretical basis for the occurrence of various blood diseases in zebrafish and other organisms.
摘要：
暴露于环境污染物经常导致血液疾病的发生，但潜在的分子机制却鲜为人知.Diflovidazin（DFD）的毒性，一种广泛使用的除螨剂，非目标生物的血液系统需要紧急阐明。探讨DFD（2、2.5和3mg/L）对造血干细胞（HSC）发育和存活的有害影响。本研究采用斑马鱼模型。DFD暴露减少了HSC及其亚型的数量，包括巨噬细胞,中性粒细胞，胸腺T细胞,红细胞,和血小板。HSCs凋亡和分化异常的显著转变是血细胞削减的主要缘由。使用小分子拮抗剂和p53吗啉代显示NF-κB/p53途径负责DFD暴露后HSC的凋亡。TLR4抑制剂和分子对接的修复结果显示,它是NF-κB信号的上游，在DFD毒理学中起着至关重要的作用。本研究阐明了DFD在斑马鱼HSC损伤中的作用及其分子机制。为斑马鱼等多种血液疾病的发生提供了理论依据。
