Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

Luthe, Gregor; Jacobus, James A.; Robertson, Larry W.

doi:10.1016/j.etap.2007.10.017

Cited by 69 publications

(41 citation statements)

References 68 publications

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“…It is pertinent to note that PCBs vary in structure with structure-activity relationship studies denoting different receptor interactions between “coplanar or dioxin-like” and “non-coplanar or phenobarbital-like” PCBs (Luthe et al 2008). In the current study, we employed two different sets of PCBs, one being PCB126 which is a prototypical “dioxin-like” congener and the other being the PCB mixture, Aroclor1260.…”

Section: Discussionmentioning

confidence: 99%

A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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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 (4.9 mg/kg) or the PCB mixture, Arcolor1260 (20 mg/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.

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Section: Discussionmentioning

confidence: 99%

A compromised liver alters polychlorinated biphenyl-mediated toxicity

et al. 2017

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“…Many biologic effects of PCBs are receptor-mediated (Luthe et al, 2008), including the well-described characteristics of PCBs as inducers of xenobiotic metabolism (Parkinson et al, 1983, Safe et al, 1985). On the other hand, PCB metabolism is generally regarded as a detoxication process due to the fact that a large proportion of all hydroxylated PCB metabolites (OH-PCBs) being formed are excreted from the body as such or after conjugation (Birnbaum, 1983, Ohta et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Metabolism and metabolites of polychlorinated biphenyls

Grimm

Kania-Korwel

et al. 2015

Critical Reviews in Toxicology

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369

414

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The metabolism of polychlorinated biphenyls (PCBs) is complex and has an impact on toxicity and thereby assessment of PCB risks. A large number of reactive and stable metabolites are formed in the processes of biotransformation in biota in general and in humans in particular. The aim of this document is to provide an overview of PCB metabolism and to identify metabolites of concern and their occurrence. Emphasis is given to mammalian metabolism of PCBs and their hydroxyl, methylsulfonyl, and sulfated metabolites, especially those that persist in human blood. Potential intracellular targets and health risks are also discussed.

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“…Epidemiologic studies have correlated PCB exposure with multiple health complications such as liver injury, hypertension and vascular inflammation (Cave et al, 2010; Perkins et al, 2016). PCBs have been shown to interact with a myriad of receptors in the body including the AhR and hepatic nuclear receptors, and this has been attributed as a mechanism of PCB-induced toxicity (Luthe et al, 2008; Wahlang et al, 2014). Furthermore, these receptors are intimately involved in maintaining energy homeostasis, cell proliferation, differentiation and inflammation by activating their target gene battery.…”

Section: Introductionmentioning

confidence: 99%

Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases

Wahlang

Petriello

Perkins

et al. 2016

Toxicology in Vitro

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Exposure to persistent organic pollutants, including polychlorinated biphenyls (PCBs) is correlated with multiple vascular complications including endothelial cell dysfunction and atherosclerosis. PCB-induced activation of the vasculature subsequently leads to oxidative stress and induction of pro-inflammatory cytokines and adhesion proteins. Gene expression of these cytokines/proteins is known to be regulated by small, endogenous oligonucleotides known as microRNAs that interact with messenger RNA. MicroRNAs are an acknowledged component of the epigenome, but the role of environmentally-driven epigenetic changes such as toxicant-induced changes in microRNA profiles are currently understudied. The objective of this study was to determine the effects of PCB exposure on microRNA expression profile in primary human endothelial cells using the commercial PCB mixture Aroclor 1260. Samples were analyzed using Affymetrix GeneChip® miRNA 4.0 arrays for high throughput detection and selected microRNA gene expression was validated (RT-PCR). Microarray analysis identified 557 out of 6658 microRNAs that were changed with PCB exposure (p <0.05). In-silico analysis using MetaCore database identified 21 of these microRNAs to be associated with vascular diseases. Further validation showed that Aroclor 1260 increased miR-21, miR-31, miR-126, miR-221 and miR-222 expression levels. Upregulated miR-21 has been reported in cardiac injury while miR-126 and miR-31 modulate inflammation. Our results demonstrated evidence of altered microRNA expression with PCB exposure, thus providing novel insights into mechanisms of PCB toxicity.

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Receptor interactions by polybrominated diphenyl ethers versus polychlorinated biphenyls: A theoretical structure–activity assessment

Cited by 69 publications

References 68 publications

A compromised liver alters polychlorinated biphenyl-mediated toxicity

A compromised liver alters polychlorinated biphenyl-mediated toxicity

Metabolism and metabolites of polychlorinated biphenyls

Polychlorinated biphenyl exposure alters the expression profile of microRNAs associated with vascular diseases

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