title: Metallothionein's role in PCB126 induced hepatotoxicity and hepatic micronutrient disruption.
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 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.
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa; Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: W D
authors.initials: WD
authors.lastname: Klaren
authors.affiliation: Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: S
authors.initials: S
authors.lastname: Flor
authors.affiliation: Department of Pathology, University of Iowa, Iowa City, Iowa.
authors.forename: K N
authors.initials: KN
authors.lastname: Gibson-Corley
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa; Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: G
authors.initials: G
authors.lastname: Ludewig
authors.affiliation: Interdisciplinary Graduate Program in Human Toxicology, University of Iowa, Iowa City, Iowa; Department of Occupational and Environmental Health, College of Public Health, University of Iowa, Iowa City, Iowa.
authors.forename: L W
authors.initials: LW
authors.lastname: Robertson
keywords: AhR; Metallothionein; Metals; Micronutrients; PCB; hepatotoxicity