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

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

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.

MeSH terms

  • Animals
  • Carrier Proteins / metabolism
  • Endoplasmic Reticulum Stress / drug effects
  • Fatty Acids, Nonesterified / metabolism
  • Fatty Liver / metabolism
  • Female
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Liver / drug effects*
  • Liver / metabolism
  • Oxidation-Reduction
  • Pilot Projects
  • Polychlorinated Biphenyls / toxicity*
  • Rats
  • Rats, Sprague-Dawley
  • Signal Transduction

Substances

  • Carrier Proteins
  • Fatty Acids, Nonesterified
  • microsomal triglyceride transfer protein
  • Polychlorinated Biphenyls
  • 3,4,5,3',4'-pentachlorobiphenyl