1. Academic Validation
  2. Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway

Diflovidazin damages the hematopoietic stem cells to zebrafish embryos via the TLR4/ NF-κB/ p53 pathway

  • Fish Shellfish Immunol. 2023 Mar 8;135:108672. doi: 10.1016/j.fsi.2023.108672.
Kun Jia 1 Haibin Xiong 1 Wei Yuan 1 Lirong Huang 1 Jiaxin Xu 1 Chen Lu 1 Ying Hu 1 Kaijie Huang 1 Qiang Luo 1 Jinze Ma 1 Huiqiang Lu 2
Affiliations

Affiliations

  • 1 Ganzhou Key Laboratory for Drug Screening and Discovery, Gannan Normal University, Ganzhou, 341000, Jiangxi, China.
  • 2 Ganzhou Key Laboratory for Drug Screening and Discovery, Gannan Normal University, Ganzhou, 341000, Jiangxi, China; Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Jiangxi Key Laboratory of Developmental Biology of Organs, Affiliated Hospital of Jinggangshan University, Ji'an, 343009, China. Electronic address: luhq2@126.com.
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.

Keywords

Blood diseases; Diflovidazin; Hematopoietic stem cells; Immunotoxicity; TLR4/ NF-κB/ p53 pathway.

Figures
Products
Inhibitors & Agonists
Other Products