Abstract
N-(1,3-dimethylbutyl)-N'-phenyl-p-phenylenediamine quinone(6PPDQ)has attracted significant atten-tion due to its highly acute lethality to sensitive salmonids.However,studies investigating the mecha-nisms underlying its acute toxicity have been lacking.In this work,we demonstrated the sensitivity of rainbow trout to 6PPDQ-induced mortality.Moribund trout exhibited significantly higher brain concen-trations of 6PPDQ compared to surviving trout.In an in vitro model using human brain microvascular endothelial cells,6PPDQ can penetrate the blood-brain barrier and enhance blood-brain barrier perme-ability without compromising cell viability.The time spent in the top of the tank increased with rising 6PPDQ concentrations,as indicated by locomotion behavior tests.Furthermore,6PPDQ influenced neuro-transmitter levels and mRNA expression of neurotransmission-related genes in the brain and exhibited strong binding affinity to target neurotransmission-related proteins using computational simulations.The integrated biomarker response value associated with neurotoxicity showed a positive linear correla-tion with trout mortality.These findings significantly contribute to filling the knowledge gap between neurological impairments and apical outcomes,including behavioral effects and mortality,induced by 6PPDQ.
基金项目
国家自然科学基金(42177254)
广东省自然科学基金(2020B1212030008)
NETL
NSTL
万方数据