@article{ca16bfa42a4241958073bcf04c0cbc4b,
title = "Neurological impairment is crucial for tire rubber-derived contaminant 6PPDQ-induced acute toxicity to rainbow trout",
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.",
keywords = "Emerging contaminant, Locomotor activity, Molecular dynamics simulation, Neurotransmission, Rainbow trout",
author = "Liao, {Xiao Liang} and Chen, {Zhi Feng} and Ou, {Shi Ping} and Liu, {Qian Yi} and Lin, {Shan Hong} and Zhou, {Jia Ming} and Yujie Wang and Zongwei Cai",
note = "This work was supported by the National Natural Science Foundation of China (42177254) and Science and Technology Planning Project of Guangdong Province (2020B1212030008). We are grateful to B. Wang (Heilongjiang River Fishery Research Institute, Chinese Academy of Fishery Sciences) for his assistance with rainbow trout acquisition and maintenance. We thank S. Lu (Guangdong University of Technology) for helping us conduct molecular dynamics simulation. We thank LetPub (www.letpub.com) for its linguistic assistance during the preparation of this manuscript. Zhi-Feng Chen, Zongwei Cai, and Xiao-Liang Liao designed the study; Zhi-Feng Chen and Zongwei Cai received funding for the research; Xiao-Liang Liao and Zhi-Feng Chen performed the exposure experiments; Xiao-Liang Liao, Qian-Yi Liu, and Jia-Ming Zhou conducted the sample pretreatment and analyses; Xiao-Liang Liao and Shan-Hong Lin carried out the behavioral experiments; Shi-Ping Ou performed the in vitro blood–brain barrier experiments; Xiao-Liang Liao performed the computational analyses; Xiao-Liang Liao, Shi-Ping Ou, and Zhi-Feng Chen conducted the statistical analyses; Zhi-Feng Chen, Yujie Wang, and Xiao-Liang Liao interpreted the RT-qPCR and molecular dynamics simulation data; Zhi-Feng Chen and Xiao-Liang Liao drafted the initial manuscript, with all authors contributing to subsequent editing and final approval. Publisher Copyright: {\textcopyright} 2023 Science China Press",
year = "2024",
month = mar,
day = "15",
doi = "10.1016/j.scib.2023.12.045",
language = "English",
volume = "69",
pages = "621--635",
journal = "Science Bulletin",
issn = "2095-9273",
publisher = "Elsevier BV",
number = "5",
}
