Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway. Issue 135 (April 2023)

• Record Type: Journal Article
• Authors: Jia, Kun; Xiong, Haibin; Yuan, Wei; Huang, Lirong; Xu, Jiaxin; Lu, Chen; Hu, Ying; Huang, Kaijie; Luo, Qiang; Ma, Jinze; Lu, Huiqiang
• Is Part Of: Fish & shellfish immunology. Issue 135(2023)
• Publication Date: 2023-04
• Subjects: Diflovidazin -- Hematopoietic stem cells -- TLR4/ NF-κB/ p53 pathway -- Blood diseases -- Immunotoxicity; DFD Diflovidazin -- HSCs hematopoietic stem cells -- TLR4 Toll-like receptor 4 -- CHT caudal hematopoietic tissue -- LC50 median lethal concentration 50% -- hpf hour post-fertilization -- QC Quinoclamine -- CQ Chloroquine -- PCNA proliferation cell nuclear antigen -- TUNEL TdT-mediated dUTP nick end labeling; Fishes -- Immunology -- Periodicals; Shellfish -- Immunology -- Periodicals; Poissons -- Immunologie -- Périodiques; Crustacés -- Immunologie -- Périodiques; 571.9617
• DOI: 10.1016/j.fsi.2023.108672
• Languages: English
• ISSNs: 1050-4648

Abstract

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. Graphical abstract: Image 1 Highlights: DFD damaged the normal development of zebrafish embryo. DFD induced the apoptosis of hematopoietic stem cells and hematopoietic defects. DFD might cause immunotoxicity of zebrafish. DFD regulated the TLR4/NF-κB/p53 pathway specifically.