Liver metabolic disruption induced after a single exposure to PCB126 in rats

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• 作者：Natalie A. Chapados ; Marie-Pier Boucher
• 关键词：Hepatic steatosis ; Rats ; Inflammation ; Unfolded protein response ; PCB126
• 刊名：Environmental Science and Pollution Research
• 出版年：2017
• 出版时间：January 2017
• 年：2017
• 卷：24
• 期：2
• 页码：1854-1861
• 全文大小：
• 刊物类别：Earth and Environmental Science
• 刊物主题：Environment, general; Environmental Chemistry; Ecotoxicology; Environmental Health; Atmospheric Protection/Air Quality Control/Air Pollution; Waste Water Technology / Water Pollution Control / Water M
• 出版者：Springer Berlin Heidelberg
• ISSN：1614-7499
• 卷排序：24

文摘

Polychlorinated biphenyls (PCBs) have been recognized as metabolic disruptors. The liver plays a pivotal role in detoxification of an organism. Fatty liver results from altered intra-, and extra-hepatic mediators and is associated with increased glucose-related protein 78 (GRP78), commonly used as a marker for endoplasmic reticulum (ER) stress signaling. This pilot study aimed to study the effects of a single exposure on fatty liver metabolic parameters. The objective of the study is to characterize the effects of 3,3′,4,4′,5-pentachlorobiphenyl (PCB126) on ER stress protein chaperon GRP78 and CCAAT-enhancer-binding protein homologous protein (CHOP) and intra-hepatic mediators such as microsomal triglyceride transfer protein (MTP), sterol regulatory element-binding protein 1c (SREBP1c), and peroxisome proliferator-activated receptor alpha (PPARα), as well as extra-hepatic factors such as non-esterified fatty acid (NEFA) and tumor necrosis factor alpha (TNFα). Hepatic GRP78 mRNA and protein levels, indicating the presence of ER stress, were significantly increased following a single PCB126 exposure in rats. Intra-hepatic mechanisms such as lipoprotein secretion pathway (i.e., MTP), lipogenesis de novo (i.e., SREBP1c), and oxidation (i.e., PPARα) were altered in PCB126-treated rats. In addition, a state of inflammation measured by higher TNFα plasma levels was present in contaminated rats. These data indicate that a single injection of PCB126-modulated expression of GRP78 associated with hepatic ER stress and systemic inflammation in rats.