Carbendazim led to neurological abnormalities by interfering metabolic profiles in zebrafish brain after short-term exposure

Carbendazim is an agricultural fungicide and a widely present ecotoxic pollutant, but its damaging effects on the nervous system are not fully understood. Here, we assessed effects of short-term exposure to carbendazim on zebrafish brains. It has been revealed firstly that carbendazim can accumulate in the brain after a 7-day exposure, with the maximum concentration of 68.22 ± 9.84 μg/kg, which caused tissue vacuolization and neuronal damage, then led to a decline in motor behavioral abilities, especially a significant reduction in the distance moved. These changes may be attributed to metabolism abnormalities. Based on metabolomics and lipidomics, substantial alterations were observed in 264 lipids and 135 metabolites, with notable enrichment in 5 metabolic pathways, including glycerophospholipid metabolism, glycerolipid metabolism, and sphingolipid metabolism. To investigate system-level variations, weighted correlation network analysis was utilized to screen for 4 biomarkers strongly associated with carbendazim exposure: citric acid, guanosine-5′-monophosphate, sphingosine, and monoacylglycerol. The alterations of these markers confirmed damages of carbendazim to zebrafish nervous system, further elucidating that metabolic disorders caused by carbendazim in brains led to tissue damage and subsequent changes in motor behavior. This study provides scientific evidence for neurotoxicities of carbendazim and offers new insights into ecological risks. • The accumulation of carbendazim in zebrafish brain was detected for the first time. • Carbendazim caused brain structural damage and behavioral abnormalities in zebrafish. • Carbendazim impacted brain metabolic profiles, particularly lipid homeostasis. • Metabolic disorders may be the cause of neurotoxicity induced by carbendazim.