Polychlorinated biphenyl 126 exposure in rats alters skeletal muscle mitochondrial function
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In the past few years, polychlorinated biphenyls (PCBs), a class of environmental pollutants, have been associated with metabolism dysregulation. Muscle is one of the key regulators of metabolism because of its mass and its important role in terms of glucose consumption and glucose storage. It has been shown that muscle alterations, such as oxidative stress and mitochondrial dysfunction, contribute significantly to the development of metabolic diseases. No study has yet investigated the toxicological effect of PCBs on muscle mitochondrial function and oxidative stress in vivo. The aim of this study was to assess the effect of PCB126 in vivo exposure (single dose of 1.05 μmol/kg) on muscle mitochondrial function and oxidative stress in rats. PCB126-treated rats showed a marked increase in Cyp1a1 mRNA levels in skeletal muscles in association with a 40% reduction in state 3 oxygen consumption rate measured with complex I substrates in permeabilized muscle fibers. Furthermore, PCB126 exposure altered the expression of some enzymes involved in ROS detoxification such as catalase and glutaredoxin 2. Our results highlight for the first time a toxic effect of coplanar PCBs on skeletal muscle mitochondrial function and oxidative stress. This suggests that acute PCB exposure, by affecting muscle metabolism, could contribute to the development of metabolic disorders. Studies are needed to determine if lower-level but longer-term PCB exposure exhibits the same effect.
KeywordsPolychlorinated biphenyls Oxidative phosphorylation Electron transport chain Oxidative stress Skeletal muscle metabolism
Experiments were performed in Dr. Aguer’s laboratory at the Institut du Savoir Monfort - Recherche (Ottawa, ON, Canada), except for the q-PCR experiment that was performed in Dr. Atlas’s laboratory at Health Canada. Conception and design of the experiments: NC and CA; collection, assembly, analysis, and interpretation of data: CTL, LG, JFM, VP, ASN, NC, and CA; drafting the article or revising it critically for important intellectual content: CTL, LG, JFM, VP, EA, ASN, NC, and CA; approval of the final version: CTL, LG, JFM, VP, EA, ASN, NC and CA.
This work was supported by operating funding from the Institut du Savoir Montfort - Recherche to CA, NSERC (Natural Sciences and Engineering Research Council of Canada) Discovery grants [grant numbers 2015-06263 to CA and 418312-2012 to NC], and Chemical Management Plan from Health Canada to EA. Undergraduate Research Opportunity Program (UROP) scholarship to CTL was provided by the University of Ottawa.
Compliance with ethical standards
The protocol was approved by the Animal Care Committee of the University of Ottawa (ME-2230) and performed in compliance with the Canadian council on Animal Care guidelines.
Conflict of interest
The authors declare that they have no competing interests.
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