研究人员证明了虹鳟鱼对6PPDQ(N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone)诱导的死亡的敏感性。与存活的鳟鱼相比,奄奄一息的鳟鱼大脑中6PPDQ的浓度明显更高。在使用人脑微血管内皮细胞的体外模型中,6PPDQ 可以穿透血脑屏障并增强血脑屏障的通透性,而不会损害细胞的活力。运动行为测试表明,随着6PPDQ浓度的升高,在水箱顶部停留的时间也会增加。
此外,6PPDQ还能影响脑内神经递质水平和神经递质相关基因的mRNA表达,并通过计算模拟显示出与目标神经递质相关蛋白的强结合亲和力。与神经毒性相关的综合生物标志物反应值与鳟鱼死亡率呈正线性相关。这些发现大大有助于填补6PPDQ所诱导的神经损伤和急性结果(包括行为影响和死亡率)之间的知识空白。
据悉,6PPDQ因其对敏感鲑科具有高度急性致死性而备受关注。然而,对其急性毒性机理的研究还很缺乏。
附:英文原文
Title: Neurological impairment is crucial for tire rubber-derived contaminant 6PPDQ-induced acute toxicity to rainbow trout
Author: anonymous
Issue&Volume: 2023/12/26
Abstract: N-(1,3-dimethylbutyl)-N′-phenyl-p-phenylenediamine quinone (6PPDQ) has attracted significant attention due to its highly acute lethality to sensitive salmonids. However, studies investigating the mechanisms 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 concentrations 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 permeability 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 neurotransmitter 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 correlation 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.
DOI: 10.1016/j.scib.2023.12.045
Source: https://www.sciencedirect.com/science/article/abs/pii/S2095927323009313
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