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Environ Sci Pollut Res Int. 2017 Jan;24(2):1854-1861. doi: 10.1007/s11356-016-7939-8. Epub 2016 Oct 31.

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

Author information

1
Institut de recherche de l'Hôpital Montfort, Institut du savoir Montfort, 713 Montreal Road, Pavillon E, Ottawa, Ontario, K1K 0T2, Canada. n.chapados@gmail.com.
2
Shcool of Human Kinetics, Faculty of Health Sciences, University of Ottawa, Ottawa, Ontario, Canada. n.chapados@gmail.com.
3
La Cité, Ottawa, Ontario, Canada.

Abstract

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.

KEYWORDS:

Hepatic steatosis; Inflammation; PCB126; Rats; Unfolded protein response

PMID:
27796995
DOI:
10.1007/s11356-016-7939-8
[Indexed for MEDLINE]

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