Low-dose PCB126 exposure disrupts cardiac metabolism and causes hypertrophy and fibrosis in mice

Can Wang; Ruina Cui; Congying Niu; Xiali Zhong; Qicheng Zhu; Di Ji; Xianjie Li; Hongxia Zhang; Chunqiao Liu; Lina Zhou; Yanli Li; Guowang Xu; Yanhong Wei

doi:10.1016/j.envpol.2021.118079

Low-dose PCB126 exposure disrupts cardiac metabolism and causes hypertrophy and fibrosis in mice

Environ Pollut. 2021 Dec 1:290:118079. doi: 10.1016/j.envpol.2021.118079. Epub 2021 Aug 31.

Authors

Can Wang¹, Ruina Cui², Congying Niu¹, Xiali Zhong¹, Qicheng Zhu¹, Di Ji¹, Xianjie Li¹, Hongxia Zhang², Chunqiao Liu³, Lina Zhou⁴, Yanli Li⁴, Guowang Xu⁴, Yanhong Wei⁵

Affiliations

¹ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China.
² Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, 100101, China.
³ State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, 510060, China.
⁴ CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, Dalian, 116023, China.
⁵ Guangdong Provincial Key Laboratory of Food, Nutrition and Health, Department of Toxicology, School of Public Health, Sun Yat-sen University, Guangzhou, 510080, China. Electronic address: weiyh9@mail.sysu.edu.cn.

PMID: 34488161
DOI: 10.1016/j.envpol.2021.118079

Abstract

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.

Keywords: Cardiotoxicity; Metabolic disturbance; Metabolomics; Polychlorinated biphenyls.

MeSH terms

Animals
Fibrosis
Hypertrophy
Lipid Metabolism
Male
Mice
Polychlorinated Biphenyls* / toxicity
Polychlorinated Dibenzodioxins*

Substances

Polychlorinated Dibenzodioxins
Polychlorinated Biphenyls