A compromised liver alters polychlorinated biphenyl-mediated toxicity.
Exposure to environmental toxicants namely polychlorinated biphenyls (PCBs) is correlated with multiple health disorders including liver and cardiovascular diseases. The liver is important for both xenobiotic and endobiotic metabolism. However, the responses of an injured liver to subsequent environmental insults has not been investigated. The current study aims to evaluate the role of a compromised liver in PCB-induced toxicity and define the implications on overall body homeostasis. Male C57Bl/6 mice were fed either an amino acid control diet (CD) or a methionine-choline deficient diet (MCD) during the 12-week study. Mice were subsequently exposed to either PCB126 (4.9mg/kg) or the PCB mixture, Arcolor1260 (20mg/kg) and analyzed for inflammatory, calorimetry and metabolic parameters. Consistent with the literature, MCD diet-fed mice demonstrated steatosis, indicative of a compromised liver. Mice fed the MCD-diet and subsequently exposed to PCB126 showed observable wasting syndrome leading to mortality. PCB126 and Aroclor1260 exposure worsened hepatic fibrosis exhibited by the MCD groups. Interestingly, PCB126 but not Aroclor1260 induced steatosis and inflammation in CD-fed mice. Mice with liver injury and subsequently exposed to PCBs also manifested metabolic disturbances due to alterations in hepatic gene expression. Furthermore, PCB exposure in MCD-fed mice led to extra-hepatic toxicity such as upregulated circulating inflammatory biomarkers, implicating endothelial cell dysfunction. Taken together, these results indicate that environmental pollution can exacerbate toxicity caused by diet-induced liver injury which may be partially due to dysfunctional energy homeostasis. This is relevant to PCB-exposed human cohorts who suffer from alcohol or diet-induced fatty liver diseases.
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, 40536, USA.
Banrida
B
Wahlang
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA.
Jordan T
JT
Perkins
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, 40536, USA.
Michael C
MC
Petriello
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA; Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA.
Jessie B
JB
Hoffman
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA; Department of Statistics, College of Arts and Sciences, University of Kentucky, Lexington, KY, 40536, USA.
Arnold J
AJ
Stromberg
Superfund Research Center, University of Kentucky, Lexington, KY, 40536, USA; Department of Animal and Food Sciences, College of Agriculture, Food and Environment, University of Kentucky, Lexington, KY, 40536, USA; Graduate Center for Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, KY 40536, USA. Electronic address: bhennig@uky.edu.
Bernhard
B
Hennig
D054392:Adipokines / Q000097:blood; D000818:Animals; D001140:Aroclors / Q000633:toxicity; D015415:Biomarkers / Q000097:blood; D001786:Blood Glucose / Q000378:metabolism; D002318:Cardiovascular Diseases / Q000097:blood / Q000139:chemically induced / Q000473:pathology; D002794:Choline / Q000008:administration & dosage; D004032:Diet; D004195:Disease Models, Animal; D004734:Energy Metabolism; D005234:Fatty Liver / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D015870:Gene Expression; D006706:Homeostasis / Q000187:drug effects; D007249:Inflammation / Q000097:blood / Q000139:chemically induced; D008099:Liver / Q000187:drug effects* / Q000503:physiopathology; D008103:Liver Cirrhosis / Q000097:blood / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000172:deficiency; D008810:Mice, Inbred C57BL; D011078:Polychlorinated Biphenyls / Q000633:toxicity*
D054392:Adipokines; D001140:Aroclors; D015415:Biomarkers; D001786:Blood Glucose; C026987:aroclor 1260; D008715:Methionine; D011078:Polychlorinated Biphenyls; D002794:Choline; C023035:3,4,5,3',4'-pentachlorobiphenyl
Aroclor1260; Liver; MCD; PCB126; Steatohepatitis; Toxicity