Propylparaben Induces Immunotoxicity in Zebrafish via Oxidative Stress and Gut Microbiota-Immune Axis Dysregulation
摘要
Propylparaben (PP), a widely used preservative, has an unclear immunotoxicity profile. In this study, zebrafish embryos were exposed to 2.5, 5, and 10 μM PP to investigate its developmental and immunological effects. PP induced dose-dependent developmental abnormalities and immunotoxicity. Specifically, it significantly reduced the populations of neutrophils, macrophages, and hematopoietic stem cells (HSCs) in zebrafish embryos. Mechanistically, PP suppressed the TLR4/MyD88/NF-κB pathway and pro-inflammatory cytokines (TNF-α, IL-1β, IL-6) in embryos, whereas adult zebrafish exhibited marked upregulation of this pathway and these cytokines in intestinal and splenic tissues. PP exposure also elevated reactive oxygen species (ROS) and lipid peroxidation. Co-treatment with the antioxidant astaxanthin (AST) attenuated PP-induced immunotoxicity by reducing ROS level and restoring HSCs, neutrophil, and macrophage populations, confirming oxidative stress as a key mechanism. Furthermore, PP induced gut microbiota dysbiosis and intestinal developmental defects. Exposing germ-free (GF) zebrafish embryos to PP resulted in no significant changes in neutrophils and HSCs, indicating that its immunotoxicity is microbiota-dependent. This was confirmed by fecal microbiota transplantation (FMT), where embryos receiving microbiota from PP-treated donors showed concentration-dependent decreases in neutrophils and HSCs. Our study elucidates the ecological and health risks of PP, advocating for reevaluation of preservative safety and microbiota-targeted mitigation strategies.
Yong Huang
Ph.D. student
Huan Xu
M.S. student
Liting Liu
M.S. student
Yifan Sun
M.S. student
Xiaochang Huang
Lecturer
