Low-dose PCB126 exposure disrupts cardiac metabolism and causes hypertrophy and fibrosis in mice
| Autor: | Guowang Xu, Xiali Zhong, Ruina Cui, Yanhong Wei, Chunqiao Liu, Yanli Li, Xianjie Li, Di Ji, Hongxia Zhang, Can Wang, Lina Zhou, Qicheng Zhu, Congying Niu |
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| Rok vydání: | 2021 |
| Předmět: |
Male
medicine.medical_specialty Polychlorinated Dibenzodioxins Cardiac fibrosis Health Toxicology and Mutagenesis Linoleic acid Toxicology Muscle hypertrophy chemistry.chemical_compound Mice Fibrosis Internal medicine medicine Animals chemistry.chemical_classification Cardiotoxicity Chemistry Lipid metabolism General Medicine Metabolism Hypertrophy medicine.disease Lipid Metabolism Pollution Polychlorinated Biphenyls Amino acid Endocrinology |
| Zdroj: | Environmental pollution (Barking, Essex : 1987). 290 |
| ISSN: | 1873-6424 |
| Popis: | The residue of polychlorinated biphenyls (PCBs) exists throughout the environment and humans are subject to long-term exposure. As such, the potential environmental and health risk caused by low-dose exposure to PCBs has attracted much attention. 3, 3′, 4, 4′, 5-pentachlorobiphenyl (PCB126), the highest toxicity compound among dioxin-like-PCBs, has been widely used and mass-produced. Cardiotoxicity is PCB126's crucial adverse effect. Maintaining proper metabolism underlies heart health, whereas the impact of PCB126 exposure on cardiac metabolic patterns has yet to be elucidated. In this study, we administered 0.5 and 50 μg/kg bw of PCB126 to adult male mice weekly by gavage for eight weeks. Pathological results showed that low-dose PCB126 exposure induced heart injury. Metabolomic analysis of the heart tissue exposed to low-dose PCB126 identified 59 differential metabolites that were involved in lipid metabolism, amino acid metabolism, and the tricarboxylic acid (TCA) cycle. Typical metabolomic characteristic of cardiac hypertrophy was reflected by accumulation of fatty acids (e.g. palmitic, palmitoleic, and linoleic acid), and disturbance of carbohydrates including D-glucose and intermediates in TCA cycle (fumaric, succinic, and citric acid). Low-dose PCB126 exposure increased glycine and threonine, the amino acids necessary for the productions of collagen and elastin. Besides, PCB126-exposed mice exhibited upregulation of collagen synthesis enzymes and extracellular matrix proteins, indicative of cardiac fibrosis. Moreover, the expression of genes related to TGFβ/PPARγ/MMP-2 signaling pathway was perturbed in the PCB126-treated hearts. Together, our results reveal that low-dose PCB126 exposure disrupts cardiac metabolism correlated with hypertrophy and fibrosis. This study sheds light on the underlying mechanism of PCBs' cardiotoxicity and identifies potential sensitive biomarkers for environmental monitoring. |
| Databáze: | OpenAIRE |
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