Exploring the adverse effects of 1,3,6,8-tetrabromo-9H-carbazole in atherosclerotic model mice by metabolomic profiling integrated with mechanism studies in vitro

被引：0
|
作者：
Xu T. [1 ,2 ,4 ]
Jiang Y. [3 ]
Fu H. [1 ,2 ]
Yang G. [1 ,2 ]
Hu X. [1 ,2 ]
Chen Y. [1 ,2 ]
Zhang Q. [5 ]
Wang Y. [3 ]
Wang Y. [3 ]
Xie H.Q. [1 ,2 ]
Han F. [4 ]
Xu L. [1 ,2 ]
Zhao B. [1 ,2 ]
机构：
[1] State Key Laboratory of Environmental Chemistry and Ecotoxicology, Research Center for Eco-Environmental Sciences, Chinese Academy of Sciences, Beijing
[2] University of Chinese Academy of Sciences, Beijing
[3] Department of Preventive Medicine, Fujian Provincial Key Laboratory of Environment Factors and Cancer, Key Laboratory of Environment and Health, School of Public Health, Fujian Medical University, Fuzhou
[4] PET/CT Center, Key Laboratory of Functional Molecular Imaging, Affiliated Zhongshan Hospital of Dalian University, Dalian
[5] Department of Cardiology, Beijing Hospital, National Center of Gerontology, Beijing
来源：
Chemosphere | 2024年 / 349卷
基金：
中国国家自然科学基金;
关键词：
1,3,6,8-Tetrabromo-9H-carbazole; Atherosclerosis; Atherosclerotic model mice; Energy metabolism; Metabolomics; Reactive oxygen species;
D O I：
10.1016/j.chemosphere.2023.140767
中图分类号：
学科分类号：
摘要：
Given its wide distribution in the environment and latent toxic effects, 1,3,6,8-tetrabromo-9H-carbazole (1368-BCZ) is an emerging concern that has gained increasing attention globally. 1368-BCZ exposure is reported to have potential cardiovascular toxicity. Although atherosclerosis is a cardiovascular disease and remains a primary cause of mortality worldwide, no evidence has been found regarding the impact of 1368-BCZ on atherosclerosis. Therefore, we aimed to explore the deleterious effects of 1368-BCZ on atherosclerosis and the underlying mechanisms. Serum samples from 1368-BCZ-treated atherosclerotic model mice were subjected to metabolomic profiling to investigate the adverse influence of the pollutant. Subsequently, the molecular mechanism associated with the metabolic pathway of atherosclerotic mice that was identified following 1368-BCZ exposure was validated in vitro. Serum metabolomics analysis revealed that 1368-BCZ significantly altered the tricarboxylic acid cycle, causing a disturbance in energy metabolism. In vitro, we further validated general markers of energy metabolism based on metabolome data: 1368-BCZ dampened adenosine triphosphate (ATP) synthesis and increased reactive oxygen species (ROS) production. Furthermore, blocking the aryl hydrocarbon receptor (AhR) reversed the high production of ROS induced by 1368-BCZ. It is concluded that 1368-BCZ decreased the ATP synthesis by disturbing the energy metabolism, thereby stimulating the AhR-mediated ROS production and presumably causing aggravated atherosclerosis. This is the first comprehensive study on the cardiovascular toxicity and mechanism of 1368-BCZ based on rodent models of atherosclerosis and integrated with in vitro models. © 2023
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