Metallothionein’s role in PCB126 induced hepatotoxicity and hepatic micronutrient disruption

W.D Klaren; S Flor; K.N Gibson-Corley; G Ludewig; L.W Robertson

doi:10.1016/j.toxrep.2015.12.001

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Metallothionein’s role in PCB126 induced hepatotoxicity and hepatic micronutrient disruption

Journal article

Open access

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Metallothionein’s role in PCB126 induced hepatotoxicity and hepatic micronutrient disruption

W.D Klaren, S Flor, K.N Gibson-Corley, G Ludewig and L.W Robertson

Toxicology reports, Vol.3, pp.21-28

01/31/2016

DOI: 10.1016/j.toxrep.2015.12.001

PMCID: PMC4710377

PMID: 26770886

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Abstract

Polychlorinated biphenyls (PCBs), industrial chemicals and persistent environmental pollutants, are found in rural and urban settings. Rodent studies have shown that exposure to PCB126, a dioxin-like PCB, causes a significant disruption of hepatic micronutrient homeostasis and an increase in metallothionein (MT), an antioxidant protein and metal carrier. A MT knockout mouse strain was used to assess metallothionein’s role in micronutrient disruption and overall hepatotoxicity. Twenty four 129S male mice (12 wild type (WT) and 12 MT knockout (MTKO)) were placed on a purified diet (AIN-93G) for 3 weeks to achieve hepatic metal equilibrium. Mice were then given a single IP injection of either vehicle or 150 μmol/kg PCB126 in vehicle. The animals were sacrificed 2 weeks later and organs processed for analysis. Liver histology, hepatic lipids, gene expression, micronutrient and ROS status were investigated. Liver weights, liver lipids, ROS, and hepatocyte vacuolation were increased with PCB126 exposure along with AhR responsive genes. The MTKO animals had more severe histological changes in the liver and elevated liver lipids than their wild type counterparts. Hepatic and renal metals levels (Cu, Zn, Se and Mn) were mostly reduced by PCB126 treatment. Renal micronutrients were more affected by PCB126 treatment in the MTKO animals. This research suggests that MT may not be the sole/primary cause of the metal disruption caused by PCB126 exposure in mice, but may provide protection against overall hepatotoxicity.

Micronutrients

3,3′,4,4′,5-pentachlorobiphenyl PCB126 (PubChem CID63090)

Metals

AhR

Hepatotoxicity

Metallothionein

PCB

ISRP Project 1 2015-2020

Synthesis Core

Details

Title: Subtitle: Metallothionein’s role in PCB126 induced hepatotoxicity and hepatic micronutrient disruption
Creators: W.D Klaren - Department of Pathology, University of Iowa, Iowa City, IA, United States
S Flor - Department of Pathology, University of Iowa, Iowa City, IA, United States
K.N Gibson-Corley - Department of Pathology, University of Iowa, Iowa City, IA, United States
G Ludewig - Department of Pathology, University of Iowa, Iowa City, IA, United States
L.W Robertson - Department of Pathology, University of Iowa, Iowa City, IA, United States
Resource Type: Journal article
Publication Details: Toxicology reports, Vol.3, pp.21-28
DOI: 10.1016/j.toxrep.2015.12.001
PMID: 26770886
PMCID: PMC4710377
NLM abbreviation: Toxicol Rep
ISSN: 2214-7500
eISSN: 2214-7500
Publisher: Elsevier
Grant note: name: NIH, award: P42 ES013661; name: Training Core of the Iowa Superfund Research program, award: P42 ES013661
Language: English
Date published: 01/31/2016
Academic Unit: Occupational and Environmental Health; Pathology; Radiation Oncology; Iowa Superfund Research Program; Ophthalmology and Visual Sciences
Record Identifier: 9983997455302771

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