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

Toxicology Reports
W D KlarenL W Robertson

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 umol/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 ...Continue Reading

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Citations

May 22, 2016·Toxicological Sciences : an Official Journal of the Society of Toxicology·Xianai WuHans-Joachim Lehmler
Dec 8, 2017·Toxicological Sciences : an Official Journal of the Society of Toxicology·Michael C PetrielloAndrew J Morris

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Methods Mentioned

BETA
PCR
Assay
electrophoresis

Software Mentioned

GraphPad Prism
SAS

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