3,5-Dibromo-4-hydroxybenzaldehyde induced neurodevelopmental defects via endoplasmic reticulum stress-mediated...

Drinking water disinfection is crucial for public health safety. However, the chlorination process generates substantial amounts of DBPs that may pose significant health risks to human populations. 3,5-Dibromo-4-hydroxybenzaldehyde (DCHB) has been shown to reduce the viability of neuroblastoma cells, but its neurotoxicity has not been further evaluated. This study represents the first comprehensive evaluation of DCHB-induced neurodevelopmental toxicity using a zebrafish model, systematically characterizing its neurodevelopmental toxicity. DCHB induced abnormal brain development during the early stage of zebrafish development, and the movement behavior of the juvenile fish was also affected. Further investigations revealed that DCHB can significantly inhibited zebrafish neurodevelopment, induced cerebrovascular morphological disruption, and caused microglial reduction with abnormal cellular morphologies. Transcriptome sequencing coupled with qPCR validation demonstrated that DCHB likely triggers neurodevelopmental impairment through endoplasmic reticulum (ER) stress-mediated apoptotic pathways. Subsequent rescue experiments using the ER stress inhibitor Azoramide partly rescued DCHB-induced neurodevelopmental impairments in zebrafish. Further researchs demonstrated that chronic exposure to 2 μg/L DCHB induced behavioral impairments in adult zebrafish.This study assessed the molecular mechanisms underlying DCHB's neurodevelopmental toxicity and provided important insights for future research on potential health risks posed by DBPs and informing regulatory decision-making regarding DBP control.