scholarly journals Global marine pollutants inhibit P-glycoprotein: Environmental levels, inhibitory effects, and cocrystal structure

2016 ◽  
Vol 2 (4) ◽  
pp. e1600001 ◽  
Author(s):  
Sascha C. T. Nicklisch ◽  
Steven D. Rees ◽  
Aaron P. McGrath ◽  
Tufan Gökirmak ◽  
Lindsay T. Bonito ◽  
...  
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Specific Binding ◽  
Diphenyl Ether ◽  
Environmental Toxicants ◽  
Glycoprotein P ◽  
P Glycoprotein ◽  
Defense Protein ◽  
Cocrystal Structure

The world’s oceans are a global reservoir of persistent organic pollutants to which humans and other animals are exposed. Although it is well known that these pollutants are potentially hazardous to human and environmental health, their impacts remain incompletely understood. We examined how persistent organic pollutants interact with the drug efflux transporter P-glycoprotein (P-gp), an evolutionarily conserved defense protein that is essential for protection against environmental toxicants. We identified specific congeners of organochlorine pesticides, polychlorinated biphenyls, and polybrominated diphenyl ethers that inhibit mouse and human P-gp, and determined their environmental levels in yellowfin tuna from the Gulf of Mexico. In addition, we solved the cocrystal structure of P-gp bound to one of these inhibitory pollutants, PBDE (polybrominated diphenyl ether)–100, providing the first view of pollutant binding to a drug transporter. The results demonstrate the potential for specific binding and inhibition of mammalian P-gp by ubiquitous congeners of persistent organic pollutants present in fish and other foods, and argue for further consideration of transporter inhibition in the assessment of the risk of exposure to these chemicals.

scholarly journals Isolation of Acetobacterium sp. Strain AG, Which Reductively Debrominates Octa- and Pentabrominated Diphenyl Ether Technical Mixtures

2012 ◽  
Vol 79 (4) ◽  
pp. 1110-1117 ◽  
Author(s):  
Chang Ding ◽  
Wai Ling Chow ◽  
Jianzhong He
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Enrichment Culture ◽  
Diphenyl Ether ◽  
Environmental Pollutants ◽  
Content Type ◽  
Diphenyl Ethers ◽  
First Time ◽  
Free Enrichment

ABSTRACTPolybrominated diphenyl ethers (PBDEs) are a class of environmental pollutants that have been classified as persistent organic pollutants since 2009. In this study, a sediment-free enrichment culture (culture G) was found to reductively debrominate octa- and penta-BDE technical mixtures to less-brominated congeners (tetra-, tri-, and di-BDEs) via apara-dominant debromination pattern for the former and a strictparadebromination pattern for the latter. Culture G could debrominate 96% of 280 nM PBDEs in an octa-BDE mixture to primarily tetra-BDEs in 21 weeks. Continuous transferring of culture G with octa-/penta-BDEs dissolved inn-nonane or trichloroethene (TCE) yielded two strains (Acetobacteriumsp. strain AG andDehalococcoidessp. strain DG) that retained debromination capabilities. In the presence of lactate but without TCE, strain AG could cometabolically debrominate 75% of 275 nM PBDEs in a penta-BDE mixture in 33 days. Strain AG shows 99% identity to its closest relative,Acetobacterium malicum. In contrast to strain AG, strain DG debrominated PBDEs only in the presence of TCE. In addition, 18 out of 19 unknown PBDE debromination products were successfully identified from octa- and penta-BDE mixtures and revealed, for the first time, a comprehensive microbial PBDE debromination pathway. As an acetogenic autotroph that rapidly debrominates octa- and penta-BDE technical mixtures,Acetobacteriumsp. strain AG adds to the still-limited understanding of PBDE debromination by microorganisms.

scholarly journals Human Excretion of Polybrominated Diphenyl Ether Flame Retardants: Blood, Urine, and Sweat Study

2017 ◽  
Vol 2017 ◽  
pp. 1-14 ◽  
Author(s):  
Shelagh K. Genuis ◽  
Detlef Birkholz ◽  
Stephen J. Genuis
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Flame Retardants ◽  
Diphenyl Ether ◽  
Body Fluids ◽  
Urine Samples ◽  
Health Implications ◽  
Reproductive Effects ◽  
Diphenyl Ethers

Commonly used as flame retardants, polybrominated diphenyl ethers (PBDEs) are routinely detected in the environment, animals, and humans. Although these persistent organic pollutants are increasingly recognized as having serious health implications, particularly for children, this is the first study, to our knowledge, to investigate an intervention for human elimination of bioaccumulated PBDEs. Objectives. To determine the efficacy of blood, urine, and perspiration as PBDE biomonitoring mediums; assess excretion of five common PBDE congeners (28, 47, 99, 100, and 153) in urine and perspiration; and explore the potential of induced sweating for decreasing bioaccumulated PBDEs. Results. PBDE congeners were not found in urine samples; findings focus on blood and perspiration. 80% of participants tested positive in one or more body fluids for PBDE 28, 100% for PBDE 47, 95% for PBDE 99, and 90% for PBDE 100 and PBDE 153. Induced perspiration facilitated excretion of the five congeners, with different rates of excretion for different congeners. Conclusion. Blood testing provides only a partial understanding of human PBDE bioaccumulation; testing of both blood and perspiration provides a better understanding. This study provides important baseline evidence for regular induced perspiration as a potential means for therapeutic PBDE elimination. Fetotoxic and reproductive effects of PBDE exposure highlight the importance of further detoxification research.

scholarly journals A Human Relevant Defined Mixture of Persistent Organic Pollutants (POPs) Affects In Vitro Secretion of Glucagon-Like Peptide 1 (GLP-1), but Does Not Affect Translocation of Its Receptor

2019 ◽  
Vol 172 (2) ◽  
pp. 359-367 ◽  
Author(s):  
Maeve Shannon ◽  
Yuling Xie ◽  
Steven Verhaegen ◽  
Jodie Wilson ◽  
Hanne F Berntsen ◽  
...  
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Complex Mixture ◽  
Blood Levels ◽  
Environmental Toxicants ◽  
Blood Concentrations ◽  
Total Mixture ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Abstract Environmental exposure to persistent organic pollutants (POPs) has been suggested as a contributing factor for the increased rate of type 2 diabetes and obesity. A complex mixture of 29 POPs (Total mixture), based on human blood concentrations, was used to expose a glucagon-like peptide 1 (GLP-1) secreting enteroendocrine cell line (pGIP/neo: STC-1) in vitro for 3 and 24 h. Significant increases of GLP-1 occurred when cells were exposed to the Total mixture at ×500 blood levels. Six sub-mixtures representing chlorinated (Cl), brominated (Br), and perfluorinated chemicals (PFAA), and their combinations (Cl + Br, Cl + PFAA, Br + PFAA) were also tested at ×500. Secretion levels seen for these remained lower than the Total mixture, and the Br mixture had no effect. After 24 h, increased secretion was seen with all mixtures at ×1 blood levels. Cytotoxicity was present for ×100 and ×500 blood levels. When tested in a GLP-1 receptor translocation assay (U2OS-GLP1R-EGFP), neither agonistic nor antagonist effects on receptor internalization were seen for any of the mixtures. We conclude individual classes of POPs, alone or in combination, can affect GLP-1 secretion and may contribute as a molecular mechanism linking environmental toxicants and diabetes.

scholarly journals Concentration Levels and Ecological Risks of Persistent Organic Pollutants in the Surface Sediments of Tianjin Coastal Area, China

2013 ◽  
Vol 2013 ◽  
pp. 1-8 ◽  
Author(s):  
Xiaoxia Lu ◽  
Chaoqi Chen ◽  
Shu Zhang ◽  
Zhen Hou ◽  
Junjun Yang
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Coastal Area ◽  
Polybrominated Diphenyl Ethers ◽  
Ecological Risks ◽  
Diphenyl Ethers ◽  
Polycyclic Aromatic ◽  
Probable Effect ◽  
Total Concentrations ◽  
Concentration Levels

Sediments were sampled from different surface water bodies in Tianjin coastal area, China, and persistent organic pollutants (POPs) including polycyclic aromatic hydrocarbons (PAHs), organochlorine pesticides (OCPs), polychlorinated biphenyls (PCBs), and polybrominated diphenyl ethers (PBDEs) were measured using GC/MS or GC/ECD. The purposes were to investigate the concentration levels of the POPs and to assess their ecological risks. The results showed that all the 16 priority PAHs were detected from the 10 sediments sampled with the total concentrations of the 16 PAHs ranging from 274.06 μg/kg to 2656.65 μg/kg, while the concentrations of the halogenated POPs were generally low except in the Dagu waste discharging river where the total concentrations of 24 OCPs, 35 PCBs, and 14 PBDEs were 3103.36 μg/kg, 87.31 μg/kg, and 13.88 μg/kg, respectively. In the studied sediments, PAHs exhibited risks to benthonic organisms; particularly the concentrations of naphthalene and/or acenaphthene exceeded their probable effect concentrations in several locations. In comparison, only in the Dagu waste discharging river, OCPs exhibited risks with the concentrations of heptachlor epoxide and lindane exceeding their probable effect concentrations. PCBs and PBDEs posed rare risks in the studied area.

scholarly journals In Utero Exposure to Persistent Organic Pollutants and Childhood Lipid Levels

Metabolites ◽  
2021 ◽  
Vol 11 (10) ◽  
pp. 657
Author(s):  
Maegan E. Boutot ◽  
Brian W. Whitcomb ◽  
Nadia Abdelouahab ◽  
Andrea A. Baccarelli ◽  
Amélie Boivin ◽  
...  
Keyword(s):  
Organic Pollutants ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Animal Studies ◽  
Human Study ◽  
Later Life ◽  
In Utero ◽  
High Density Lipoproteins ◽  
Lipid Levels ◽  
In Utero Exposures

Animal studies have shown that developmental exposures to polybrominated diphenyl ethers (PBDE) permanently affect blood/liver balance of lipids. No human study has evaluated associations between in utero exposures to persistent organic pollutants (POPs) and later life lipid metabolism. In this pilot, maternal plasma levels of PBDEs (BDE-47, BDE-99, BDE-100, and BDE-153) and polychlorinated biphenyls (PCB-138, PCB-153, and PCB-180) were determined at delivery in participants of GESTation and Environment (GESTE) cohort. Total cholesterol (TCh), triglycerides (TG), low- and high-density lipoproteins (LDL-C and HDL-C), total lipids (TL), and PBDEs were determined in serum of 147 children at ages 6–7. General linear regression was used to estimate the relationship between maternal POPs and child lipid levels with adjustment for potential confounders, and adjustment for childhood POPs. In utero BDE-99 was associated with lower childhood levels of TG (p = 0.003), and non-significantly with HDL-C (p = 0.06) and TL (p = 0.07). Maternal PCB-138 was associated with lower childhood levels of TG (p = 0.04), LDL-C (p = 0.04), and TL (p = 0.02). Our data indicate that in utero exposures to POPs may be associated with long lasting decrease in circulating lipids in children, suggesting increased lipid accumulation in the liver, a mechanism involved in NAFLD development, consistent with previously reported animal data.

Prenatal exposure to persistent organic pollutants and polybrominated diphenyl ethers in 10 Caribbean countries

2014 ◽  
Vol 133 ◽  
pp. 211-219 ◽  
Author(s):  
Martin S. Forde ◽  
Eric Dewailly ◽  
Lyndon Robertson ◽  
Elhadji A. Laouan Sidi ◽  
Suzanne Côté ◽  
...  
Keyword(s):  
Organic Pollutants ◽  
Prenatal Exposure ◽  
Persistent Organic Pollutants ◽  
Polybrominated Diphenyl Ethers ◽  
Diphenyl Ethers
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