Dicofol disrupts hematopoiesis and immune homeostasis in association with Nrf2/ARE signaling dysregulation and oxidative stress

Hematotoxicity and immunotoxicity are common adverse effects observed in fish exposed to environmental pollutants; however, the molecular mechanisms underlying these toxicities remain poorly understood. To investigate these mechanisms, zebrafish were exposed to dicofol (DCF) under environmentally relevant conditions. DCF exposure led to increased reactive oxygen species (ROS), malondialdehyde (MDA), superoxide dismutase (SOD), and catalase (CAT), and reduced nitric oxide (NO) content. Further analysis revealed a significant increase in TUNEL-positive cells in hematopoietic regions, accompanied by elevated expression of Bax/Bcl-2 , caspase-3 , and p53 . Antibody staining and Western blot (WB) analysis demonstrated that DCF impaired the nuclear factor erythroid 2-related factor 2 (Nrf2)-mediated antioxidant system. Astaxanthin (AST) treatment alleviated DCF-induced damage to hematopoietic stem cells. These results show that DCF disrupts antioxidant homeostasis, aggravates oxidative stress, and ultimately triggers apoptosis in hematopoietic stem cells, offering new insights into strategies to prevent and control pollutant-induced toxicity.