2. Academic Validation
  3. 2-Hydroxyanthraquinone exposure causes the damage of cerebrovascular and blood brain barrier in zebrafish via inducing inflammation and downregulation of the Wnt/β-catenin signaling pathway

2-Hydroxyanthraquinone exposure causes the damage of cerebrovascular and blood brain barrier in zebrafish via inducing inflammation and downregulation of the Wnt/β-catenin signaling pathway

  • Comp Biochem Physiol C Toxicol Pharmacol. 2025 Dec 10:301:110432. doi: 10.1016/j.cbpc.2025.110432.
Huimin Li 1,  Ziang Wang 2,  Suwei He 2,  Minghui Zhong 2,  Xichen Wang 2,  Weitao Hu 3,  Jingrong Tang 3,  Zhonghao Xiao 3,  Xiaowen Shi 3,  Zigang Cao 4
Affiliations

Affiliations

  • 1 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China; College of Basic Medicine, Jinggangshan University, Ji'an, 343009, China.
  • 2 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China; College of Traditional Chinese Medicine, Jinggangshan University, Ji'an, 343009, China.
  • 3 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China.
  • 4 Jiangxi Engineering Laboratory of Zebrafish Modeling and Drug Screening for Human Diseases, Key Laboratory of Jiangxi Province for Biological Invasion and Biosecurity, Jiangxi Key Laboratory of Developmental Biology of Organs and Epigenetics, College of Life Sciences, Clinical Research Center of Affiliated Hospital of Jinggangshan University, Jinggangshan University, Ji'an, 343009, China. Electronic address: [email protected].
PMID: 41386556 DOI: 10.1016/j.cbpc.2025.110432
Abstract

2-Hydroxyanthraquinone (2-hATQ), a photooxidation product of anthracene (ANT) within polycyclic aromatic hydrocarbons (PAHs), poses significant risks to ecological safety and human health. ANT is listed as a priority pollutant by the U.S. Environmental Protection Agency (EPA) due to its persistence and resistance to degradation in the environment. Consequently, 2-hATQ, inheriting these characteristics from its parent compound, is ubiquitously present in the environment and exhibits greater toxicity than ANT itself. However, research on its toxicological effects, particularly concerning cerebrovascular toxicity, remains limited. In this study, acute exposure of zebrafish embryos to various concentrations of 2-hATQ resulted in significant cerebrovascular developmental abnormalities, manifested as reduced total vascular area and decreased vessel number in the brain. Moreover, the number of brain microglia, Reactive Oxygen Species (ROS) levels, and apoptotic cell counts were markedly increased. Quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed that 2-hATQ disrupts zebrafish cerebrovascular and blood-brain barrier development by upregulating pro-inflammatory cytokines (il1β, tnf-α, NF-κB, il6) and inhibiting the Wnt/β-catenin signaling pathway (lef1, β-catenin, dkk1, wif1). The co-administration of dexamethasone or BML-284 effectively rescued the cerebrovascular damage. Furthermore, behavioral analysis demonstrated that exposed zebrafish larvae exhibited reduced locomotor activity and anxiety-like states. This study reveals for the first time the adverse effects of 2-hATQ exposure on brain vascular development in aquatic organisms, suggesting that 2-hATQ and its ANT-related derivatives may be potential risk factors for cerebrovascular diseases. Our findings reveal, for the first time, that 2-hATQ impairs cerebrovascular and BBB development through concurrent induction of inflammation and suppression of the Wnt/β-catenin pathway, identifying these as critical mechanistic events in its toxicity.

Keywords

2-Hydroxyanthraquinone; Cerebrovascular toxicity; Inflammation; PAHs; Zebrafish.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-19987
    99.99%, Wnt Signaling Activator
    Wnt