2. Academic Validation
  3. 2-Hydroxyanthraquinone induces cardiotoxicity in zebrafish via ferroptosis

2-Hydroxyanthraquinone induces cardiotoxicity in zebrafish via ferroptosis

  • Aquat Toxicol. 2025 Sep:286:107485. doi: 10.1016/j.aquatox.2025.107485.
Ziang Wang 1,  Chenkai Ge 2,  Wenbin Yuan 3,  Wenwen Zha 1,  Wanqing Chen 3,  Weirong Li 3,  Weitao Hu 3,  Qinyuan Shen 4,  Zhonghao Xiao 3,  Xiaowen Shi 3,  Huimin Li 5,  Zigang Cao 6
Affiliations

Affiliations

  • 1 College of Traditional Chinese Medicine and Pharmacy, Jinggangshan University, Ji'an, 343009, China; 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.
  • 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; School of Ophthalmology and Optometry, Wenzhou Medical University, Wenzhou, 325003, Zhejiang, 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 The Affiliated Stomatological Hospital, Jiangxi Medical College, Nanchang University, Nanchang, Jiangxi, 330006, PR China.
  • 5 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. Electronic address: lihuimin3465@163.com.
  • 6 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: zigangcao@126.com.
PMID: 40669437 DOI: 10.1016/j.aquatox.2025.107485
Abstract

2-Hydroxyanthraquinone (2-hATQ) is a photochemical oxidation product of anthracene (ANT), a polycyclic aromatic hydrocarbon. ANT is listed as a priority pollutant by the US Environmental Protection Agency (EPA) due to its resistance to degradation and persistence in the environment. Because of ANT's characteristics, 2-hATQ can also be ubiquitously present in the environment and is more toxic than its parent compound ANT, posing significant risks to environmental safety and human health. Nevertheless, there are limited studies addressing its toxicological effects, particularly concerning cardiovascular toxicity. In the present study, zebrafish embryos acutely exposed to 2-hATQ (0, 0.4, 0.8, and 1.2 mg/L) at different concentrations showed significant cardiac developmental abnormalities, as evidenced by slowing of the heart rate, pericardial edema, and the cardiac malformations. Transcriptomic Sequencing analysis and quantitative real-time polymerase chain reaction (qPCR) study showed that 2-hATQ induced cardiac Ferroptosis via disruption of the antioxidant system, glutathione depletion, increase in polyunsaturated fats and accumulation of iron ions. Co-exposure of Ferroptosis inhibitor (Fer-1) effectively rescues the morphological abnormalities of the heart. After exposing adult zebrafish to low concentration 2-hATQ for 28 days, ventricular morphology was reduced and internal structures showed partial vacuolation and fibrosis. This study reveals for the first time the negative influence of 2-hATQ exposure on the cardiac development of aquatic organisms and this discovery may offer significant insights and references for an in-depth understanding of 2-hATQ and Other ANT-related environmental risk substances.

Keywords

2-Hydroxyanthraquinone; Cardiac ferroptosis; Glutathione depletion; PAHs; Zebrafish.

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