Articles de revues : « Xenobiotic organic compounds »

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Lindblom, E., K. V. Gernaey, M. Henze et P. S. Mikkelsen. « Integrated modelling of two xenobiotic organic compounds ». Water Science and Technology 54, n^o 6-7 (1 septembre 2006) : 213–21. http://dx.doi.org/10.2166/wst.2006.620.

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This paper presents a dynamic mathematical model that describes the fate and transport of two selected xenobiotic organic compounds (XOCs) in a simplified representation of an integrated urban wastewater system. A simulation study, where the xenobiotics bisphenol A and pyrene are used as reference compounds, is carried out. Sorption and specific biological degradation processes are integrated with standardised water process models to model the fate of both compounds. Simulated mass flows of the two compounds during one dry weather day and one wet weather day are compared for realistic influent flow rate and concentration profiles. The wet weather day induces resuspension of stored sediments, which increases the pollutant load on the downstream system. The potential of the model to elucidate important phenomena related to origin and fate of the model compounds is demonstrated.

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Foroozesh, Maryam, Jayalakshmi Sridhar, Navneet Goyal et Jiawang Liu. « Coumarins and P450s, Studies Reported to-Date ». Molecules 24, n^o 8 (24 avril 2019) : 1620. http://dx.doi.org/10.3390/molecules24081620.

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Cytochrome P450 enzymes (CYPs) are important phase I enzymes involved in the metabolism of endogenous and xenobiotic compounds mainly through mono-oxygenation reactions into more polar and easier to excrete species. In addition to their role in detoxification, they play important roles in the biosynthesis of endogenous compounds and the bioactivation of xenobiotics. Coumarins, phytochemicals abundant in food and commonly used in fragrances and cosmetics, have been shown to interact with P450 enzymes as substrates and/or inhibitors. In this review, these interactions and their significance in pharmacology and toxicology are discussed in detail.

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Byrns, Geoff. « The fate of xenobiotic organic compounds in wastewater treatment plants ». Water Research 35, n^o 10 (juillet 2001) : 2523–33. http://dx.doi.org/10.1016/s0043-1354(00)00529-7.

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Pedersen, Joel A., Matt A. Yeager et I. H. (Mel) Suffet. « Xenobiotic Organic Compounds in Runoff from Fields Irrigated with Treated Wastewater ». Journal of Agricultural and Food Chemistry 51, n^o 5 (février 2003) : 1360–72. http://dx.doi.org/10.1021/jf025953q.

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NICOLELLA, C., M. ZOLEZZI, M. RABINO, M. FURFARO et M. ROVATTI. « Development of particle-based biofilms for degradation of xenobiotic organic compounds ». Water Research 39, n^o 12 (juillet 2005) : 2495–504. http://dx.doi.org/10.1016/j.watres.2005.04.016.

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Li, Jiuyi, Lele Qin, Lei Zhao, Aimin Wang, Yong Chen, Liao Meng, Zhongguo Zhang, Xiujun Tian et Yanmei Zhou. « Removal of Refractory Organics from Biologically Treated Landfill Leachate by Microwave Discharge Electrodeless Lamp Assisted Fenton Process ». International Journal of Photoenergy 2015 (2015) : 1–9. http://dx.doi.org/10.1155/2015/643708.

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Biologically treated leachate usually contains considerable amount of refractory organics and trace concentrations of xenobiotic pollutants. Removal of refractory organics from biologically treated landfill leachate by a novel microwave discharge electrodeless lamp (MDEL) assisted Fenton process was investigated in the present study in comparison to conventional Fenton and ultraviolet Fenton processes. Conventional Fenton and ultraviolet Fenton processes could substantially remove up to 70% of the refractory organics in a membrane bioreactor treated leachate. MDEL assisted Fenton process achieved excellent removal performance of the refractory components, and the effluent chemical oxygen demand concentration was lower than 100 mg L−1. Most organic matters were transformed into smaller compounds with molecular weights less than 1000 Da. Ten different polycyclic aromatic hydrocarbons were detected in the biologically treated leachate, most of which were effectively removed by MDEL-Fenton treatment. MDEL-Fenton process provides powerful capability in degradation of refractory and xenobiotic organic pollutants in landfill leachate and could be adopted as a single-stage polishing process for biologically treated landfill leachate to meet the stringent discharge limit.

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Küblbeck, Jenni, Jonna Niskanen et Paavo Honkakoski. « Metabolism-Disrupting Chemicals and the Constitutive Androstane Receptor CAR ». Cells 9, n^o 10 (15 octobre 2020) : 2306. http://dx.doi.org/10.3390/cells9102306.

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During the last two decades, the constitutive androstane receptor (CAR; NR1I3) has emerged as a master activator of drug- and xenobiotic-metabolizing enzymes and transporters that govern the clearance of both exogenous and endogenous small molecules. Recent studies indicate that CAR participates, together with other nuclear receptors (NRs) and transcription factors, in regulation of hepatic glucose and lipid metabolism, hepatocyte communication, proliferation and toxicity, and liver tumor development in rodents. Endocrine-disrupting chemicals (EDCs) constitute a wide range of persistent organic compounds that have been associated with aberrations of hormone-dependent physiological processes. Their adverse health effects include metabolic alterations such as diabetes, obesity, and fatty liver disease in animal models and humans exposed to EDCs. As numerous xenobiotics can activate CAR, its role in EDC-elicited adverse metabolic effects has gained much interest. Here, we review the key features and mechanisms of CAR as a xenobiotic-sensing receptor, species differences and selectivity of CAR ligands, contribution of CAR to regulation hepatic metabolism, and evidence for CAR-dependent EDC action therein.

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Schulten, Hans-Rolf. « Interactions of dissolved organic matter with xenobiotic compounds : Molecular modeling in water ». Environmental Toxicology and Chemistry 18, n^o 8 (août 1999) : 1643–55. http://dx.doi.org/10.1002/etc.5620180806.

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Swindoll, C. Michael, C. Marjorie Aelion, Durell C. Dobbins, Ou Jiang, Sharon C. Long et Frederic K. Pfaender. « Aerobic biodegradation of natural and xenobiotic organic compounds by subsurface microbial communities ». Environmental Toxicology and Chemistry 7, n^o 4 (avril 1988) : 291–99. http://dx.doi.org/10.1002/etc.5620070405.

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Top, Eva M., et Dirk Springael. « The role of mobile genetic elements in bacterial adaptation to xenobiotic organic compounds ». Current Opinion in Biotechnology 14, n^o 3 (juin 2003) : 262–69. http://dx.doi.org/10.1016/s0958-1669(03)00066-1.

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Baun, Anders, Lotte A. Reitzel, Anna Ledin, Thomas H. Christensen et Poul L. Bjerg. « Natural attenuation of xenobiotic organic compounds in a landfill leachate plume (Vejen, Denmark) ». Journal of Contaminant Hydrology 65, n^o 3-4 (septembre 2003) : 269–91. http://dx.doi.org/10.1016/s0169-7722(03)00004-4.

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Dionisio, Giuseppe, Maheswor Gautam et Inge Sindbjerg Fomsgaard. « Identification of Azoxystrobin Glutathione Conjugate Metabolites in Maize Roots by LC-MS ». Molecules 24, n^o 13 (5 juillet 2019) : 2473. http://dx.doi.org/10.3390/molecules24132473.

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Xenobiotic detoxification in plant as well as in animals has mostly been studied in relationship to the deactivation of the toxic residues of the compound that, surely for azoxystrobin, is represented by its β-methoxyacrylate portion. In maize roots treated for 96 h with azoxystrobin, the fungicide accumulated over time and detoxification compounds or conjugates appeared timewise. The main detoxified compound was the methyl ester hydrolysis product (azoxystrobin free acid, 390.14 m/z) thought to be inactive followed by the glutathione conjugated compounds identified as glutathione conjugate (711.21 m/z) and its derivative lacking the glycine residue from the GSH (654.19 m/z). The glycosylated form of azoxystrobin was also found (552.19 m/z) in a minor amount. The identification of these analytes was done by differential untargeted metabolomics analysis using Progenesis QI for label free spectral counting quantification and MS/MS confirmation of the compounds was carried out by either Data Independent Acquisition (DIA) and Data Dependent Acquisition (DDA) using high resolution LC-MS methods. Neutral loss scanning and comparison with MS/MS spectra of azoxystrobin by DDA and MSe confirmed the structures of these new azoxystrobin GSH conjugates.

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Baun, A., E. Eriksson, A. Ledin et P. S. Mikkelsen. « A methodology for ranking and hazard identification of xenobiotic organic compounds in urban stormwater ». Science of The Total Environment 370, n^o 1 (octobre 2006) : 29–38. http://dx.doi.org/10.1016/j.scitotenv.2006.05.017.

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Beldean-Galea, Mihail, Jerome Vial et Didier Thiebaut. « Development of a screening method for the determination of xenobiotic organic pollutants in municipal landfill leachate using solvent extraction and comprehensive GCxGC-qMS analysis ». Open Chemistry 11, n^o 10 (1 octobre 2013) : 1563–74. http://dx.doi.org/10.2478/s11532-013-0298-0.

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AbstractIn the present study, we propose a method for the evaluation of different classes of xenobiotic organic compounds enclosed in the municipal landfill leachate using comprehensive two-dimensional gas chromatography coupled with quadrupole mass spectrometry (GCxGC-qMS). Here we show that, due to high peak capacity of comprehensive two-dimensional gas chromatography, in a single run it is possible to separate compounds with different physical-chemical properties (such as aliphatic and aromatic compounds, polyaromatic hydrocarbons, phenols, phthalates, aldehydes, ketones, nitrogen containing compounds, organo-phosphoric flame retardants etc.), compounds which have proved to be endocrine disruptors, compounds that are persistent, bioaccumulative and toxic, carcinogenic, mutagenic, teratogenic, reprotoxic or harmful for the environment. Even though a solvent extraction method has been optimised, the extraction step still remains the main problem for a comprehensive characterization of all classes of organic toxicants enclosed in the municipal landfill leachate.

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Jacobsen, B. N., et T. Guildal. « Novel aspects for management of xenobiotic compounds in wastewater treatment plants – linking theory, field studies, regulation, engineering, and experience ». Water Science and Technology 42, n^o 7-8 (1 octobre 2000) : 315–22. http://dx.doi.org/10.2166/wst.2000.0584.

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Management aspects for control of environmental contaminants has widened from being focussed on heavy metals to a broader approach including specific organic compounds, inhibition of sensitive bacteria or algae, and newly identified environmental issues, e.g., endocrine disruption and antibiotic resistance. Studies conducted at the Avedøre WWTP confirm the relevance of such newly discovered environmental problems, however, the order of magnitude of the effects do not seem alarming. It is recommended in future research to establish links between occurrence of specific organic compounds and heavy metals to various measures of toxicity and bioaccumulation. Also data for specific biodegradation rates in WWTPs represent a bottleneck for simulating fate of specific organic compounds in the plants.

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Baun, A., A. Ledin, L. A. Reitzel, P. L. Bjerg et T. H. Christensen. « Xenobiotic organic compounds in leachates from ten Danish MSW landfills—chemical analysis and toxicity tests ». Water Research 38, n^o 18 (novembre 2004) : 3845–58. http://dx.doi.org/10.1016/j.watres.2004.07.006.

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Maya-Altamira, L., E. Eriksson et A. Baun. « Source Analysis and Hazard Screening of Xenobiotic Organic Compounds in Wastewater from Food-Processing Industries ». Water, Air, & ; Soil Pollution : Focus 8, n^o 5-6 (28 août 2008) : 505–17. http://dx.doi.org/10.1007/s11267-008-9179-5.

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Manousi, Natalia, Orfeas-Evangelos Plastiras, Natasa Kalogiouri, Constantinos Zacharis et George Zachariadis. « Metal-Organic Frameworks in Bioanalysis : Extraction of Small Organic Molecules ». Separations 8, n^o 5 (4 mai 2021) : 60. http://dx.doi.org/10.3390/separations8050060.

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The quantitative determination of xenobiotic compounds, as well as biotics in biological matrices, is generally described with the term bioanalysis. Due to the complexity of biofluids, in combination with the low concentration of the small molecules, their determination in biological matrices is a challenging procedure. Apart from the conventional solid-phase extraction, liquid-liquid extraction, protein precipitation, and direct injection approaches, nowadays, a plethora of microextraction and miniaturized extraction techniques have been reported. Furthermore, the development and evaluation of novel extraction adsorbents for sample preparation has become a popular research field. Metal-organic frameworks (MOFs) are novel materials composed of metal ions or clusters in coordination with organic linkers. Unequivocally, MOFs are gaining more and more attention in analytical chemistry due to their superior properties, including high surface area and tunability of pore size and functionality. This review discusses the utilization of MOFs in the sample preparation of biological samples for the green extraction of small organic molecules. Their common preparation and characterization strategies are discussed, while emphasis is given to their applications for green sample preparation.

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Simon, Francis R., Mieko Iwahashi, Ling-Jia Hu, Ishtiaq Qadri, Irwin M. Arias, Daniel Ortiz, Rolf Dahl et Eileen Sutherland. « Hormonal regulation of hepatic multidrug resistance-associated protein 2 (Abcc2) primarily involves the pattern of growth hormone secretion ». American Journal of Physiology-Gastrointestinal and Liver Physiology 290, n^o 4 (avril 2006) : G595—G608. http://dx.doi.org/10.1152/ajpgi.00240.2005.

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Biliary excretion is the rate-limiting step in transfer of bilirubin, other organic anions, and xenobiotics across the liver. Multidrug resistance-associated protein 2 (Mrp2, Abcc2) is the major transporter for conjugated endo- and xenobiotic-conjugated compounds into bile. Hormones regulate bilirubin and xenobiotic secretion into bile, which have dimorphic differences. Therefore, we examined the possible role of sex steroids and growth hormone in the regulation of Mrp2. In ∼8-wk-old rats, mRNA, transcriptional activity, and hepatic content of Mrp2 were selectively increased fourfold ( P < 0.001) in females compared with males. In males, estrogens increased and testosterone decreased Mrp2 mRNA and protein, whereas no significant effect was measured in females, suggesting either a direct effect on the liver or an alteration in growth hormone secretory pattern. After hypophysectomy, Mrp2 mRNA was markedly reduced and the effects of estrogens and testosterone on Mrp2 were prevented, supporting the role of pituitary hormones in controlling Mrp2 expression. Mrp2 increased following growth hormone infusion in males. Mrp2 mRNA was decreased in growth hormone-deficient “Little” mice. Growth hormone infusions in hypophysectomized rats partially restored Mrp2 levels, whereas thyroxine addition returned Mrp2 mRNA and protein to basal levels. Morphology as well as biochemical measurements demonstrated that Mrp2 was localized to the bile canaliculus in equal density in both genders, whereas hormone replacements increased Mrp2 in hypophysectomized animals. In cultured hepatocytes, thyroxine did not have an effect, but growth hormone alone and combined with thyroxine increased Mrp2 mRNA levels. In conclusion, Mrp2 levels are regulated by the combination of thyroxine and different growth hormone secretory patterns.

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Skibiński, Robert, Jakub Trawiński et Maciej Gawlik. « Characterization of Phase I Hepatic Metabolites of Anti-Premature Ejaculation Drug Dapoxetine by UHPLC-ESI-Q-TOF ». Molecules 26, n^o 13 (22 juin 2021) : 3794. http://dx.doi.org/10.3390/molecules26133794.

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Determination of the metabolism pathway of xenobiotics undergoing the hepatic pass is a crucial aspect in drug development since the presence of toxic biotransformation products may result in significant side effects during the therapy. In this study, the complete hepatic metabolism pathway of dapoxetine established according to the human liver microsome assay with the use of a high-resolution LC–MS system was described. Eleven biotransformation products of dapoxetine, including eight metabolites not reported in the literature so far, were detected and identified. N-dealkylation, hydroxylation, N-oxidation and dearylation were found to be the main metabolic reactions for the investigated xenobiotic. In silico analysis of toxicity revealed that the reaction of didesmethylation may contribute to the increased carcinogenic potential of dapoxetine metabolites. On the other hand, N-oxidation and aromatic hydroxylation biotransformation reactions possibly lead to the formation of mutagenic compounds.

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Miller, David S., Claudia Graeff, Lucy Droulle, Stefanie Fricker et Gert Fricker. « Xenobiotic efflux pumps in isolated fish brain capillaries ». American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 282, n^o 1 (1 janvier 2002) : R191—R198. http://dx.doi.org/10.1152/ajpregu.00305.2001.

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To identify specific transporters that drive xenobiotics from the central nervous system to blood, the accumulation of fluorescent drugs was studied in isolated capillaries from killifish and dogfish shark brain using confocal microscopy and quantitative image analysis. In killifish brain capillaries, luminal accumulation of fluorescent derivatives of cyclosporin A and verapamil was concentrative, specific, and energy dependent (inhibition by KCN). Transport was reduced by PSC-833, but not by leukotriene C4, indicating the involvement of P-glycoprotein. The ability of capillaries to transport the cyclosporin A derivative was unchanged over 20 h, demonstrating the long-term viability of the preparation. Luminal accumulation of the fluorescent organic anions sulforhodamine 101 and fluorescein-methotrexate was also concentrative, specific, and energy dependent. Transport of these compounds was reduced by leukotriene C4, but not by PSC-833, indicating the involvement of a multidrug resistance-associated protein (Mrp). Similar results were obtained for isolated capillaries from dogfish shark. Immunostaining localized P-glycoprotein and Mrp2 to the luminal surface of the killifish brain capillary endothelium. These findings validate a new and long-lived comparative model for studying drug transport across the blood-brain barrier and, as in mammals, implicate P-glycoprotein and Mrp2 in transport from the central nervous system to blood in fish.

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Ventorino, Valeria, Filomena Sannino, Alessandro Piccolo, Valeria Cafaro, Rita Carotenuto et Olimpia Pepe. « Methylobacterium populiVP2 : Plant Growth-Promoting Bacterium Isolated from a Highly Polluted Environment for Polycyclic Aromatic Hydrocarbon (PAH) Biodegradation ». Scientific World Journal 2014 (2014) : 1–11. http://dx.doi.org/10.1155/2014/931793.

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The use of microorganisms to accelerate the natural detoxification processes of toxic substances in the soil represents an alternative ecofriendly and low-cost method of environmental remediation compared to harmful incineration and chemical treatments. Fourteen strains able to grow on minimal selective medium with a complex mixture of different classes of xenobiotic compounds as the sole carbon source were isolated from the soil of the ex-industrial site ACNA (Aziende Chimiche Nazionali Associate) in Cengio (Savona, Italy). The best putative degrading isolate,Methylobacterium populiVP2, was identified using a polyphasic approach on the basis of its phenotypic, biochemical, and molecular characterisation. Moreover, this strain also showed multiple plant growth promotion activities: it was able to produce indole-3-acetic acid (IAA) and siderophores, solubilise phosphate, and produce a biofilm in the presence of phenanthrene and alleviate phenanthrene stress in tomato seeds. This is the first report on the simultaneous occurrence of the PAH-degrading ability byMethylobacterium populiand its multiple plant growth-promoting activities. Therefore, the selected indigenous strain, which is naturally present in highly contaminated soils, is good candidate for plant growth promotion and is capable of biodegrading xenobiotic organic compounds to remediate contaminated soil alone and/or soil associated with plants.

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Vinken, R., A. Höllrigl-Rosta, B. Schmidt, A. Schäffer et P. F. X. Corvini. « Bioavailability of a nonylphenol isomer in dependence on the association to dissolved humic substances ». Water Science and Technology 50, n^o 5 (1 septembre 2004) : 277–83. http://dx.doi.org/10.2166/wst.2004.0338.

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Humic substances are important environmental components since they represent a very large part of organic compounds on earth. According to many reports, dissolved humic substances are a determinant parameter for the bioavailability of xenobiotic compounds. For the present bioavailability studies, two kinds of dissolved humic substances, a commercially available humic acid and fulvic acids isolated from peat were used. As the relevant xenobiotic, a defined branched nonylphenol isomer, 4(3′,5′-dimethyl-3′-heptyl)-phenol (p353NP) was synthesised according to Friedel-Crafts alkylation. Equilibrium dialysis studies were implemented in order to investigate the association between 14C-labelled p353NP and dissolved humic substances. The biodegradability in the presence of dissolved humic substances was examined in experiments with the nonylphenol degrading bacterium strain Sphingomonas TTNP3 and with p353NP as sole carbon source. The results showed that p353NP-humic acid associates were formed in high amounts, whereas no adducts with fulvic acids occurred. In the degradation studies with Sphingomonas TTNP3, no effects of dissolved humic substances on the bioavailability of p353NP could be observed. It was assumed that the association between nonylphenol and humic acids occurs rapidly and is reversible. Thus, the formation of "labile" complexes did not influence biodegradation rates, which were quite low.

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Barker, Allen V., et Gretchen M. Bryson. « Bioremediation of Heavy Metals and Organic Toxicants by Composting ». Scientific World JOURNAL 2 (2002) : 407–20. http://dx.doi.org/10.1100/tsw.2002.91.

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Hazardous organic and metallic residues or by-products can enter into plants, soils, and sediments from processes associated with domestic, municipal, agricultural, industrial, and military activities. Handling, ingestion, application to land or other distributions of the contaminated materials into the environment might render harm to humans, livestock, wildlife, crops, or native plants. Considerable remediation of the hazardous wastes or contaminated plants, soils, and sediments can be accomplished by composting. High microbial diversity and activity during composting, due to the abundance of substrates in feedstocks, promotes degradation of xenobiotic organic compounds, such as pesticides, polycyclic aromatic hydrocarbons (PAHs), and polychlorinated biphenyls (PCBs). For composting of contaminated soils, noncontaminated organic matter should be cocomposted with the soils. Metallic pollutants are not degraded during composting but may be converted into organic combinations that have less bioavailability than mineral combinations of the metals. Degradation of organic contaminants in soils is facilitated by addition of composted or raw organic matter, thereby increasing the substrate levels for cometabolism of the contaminants. Similar to the composting of soils in vessels or piles, the on-site addition of organic matter to soils (sheet composting) accelerates degradation of organic pollutants and binds metallic pollutants. Recalcitrant materials, such as organochlorines, may not undergo degradation in composts or in soils, and the effects of forming organic complexes with metallic pollutants may be nonpermanent or short lived. The general conclusion is, however, that composting degrades or binds pollutants to innocuous levels or into innocuous compounds in the finished product.

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Nielsen, Per H., Peter E. Holm et Thomas H. Christensen. « A field method for determination of groundwater and groundwater-sediment associated potentials for degradation of xenobiotic organic compounds ». Chemosphere 25, n^o 4 (août 1992) : 449–62. http://dx.doi.org/10.1016/0045-6535(92)90278-y.

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Baun, A., S. N. Sørensen, R. F. Rasmussen, N. B. Hartmann et C. B. Koch. « Toxicity and bioaccumulation of xenobiotic organic compounds in the presence of aqueous suspensions of aggregates of nano-C60 ». Aquatic Toxicology 86, n^o 3 (février 2008) : 379–87. http://dx.doi.org/10.1016/j.aquatox.2007.11.019.

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Boyjoo, Yash, Vishnu K. Pareek et Ming Ang. « A review of greywater characteristics and treatment processes ». Water Science and Technology 67, n^o 7 (1 avril 2013) : 1403–24. http://dx.doi.org/10.2166/wst.2013.675.

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This paper presents a comprehensive literature review of different characteristics of greywater (GW) and current treatment methods. GW is domestic wastewater excluding toilet waste and can be classified as either low-load GW (excluding kitchen and laundry GW) or high-load GW (including kitchen and/or laundry). This review provides information on the quantity of GW produced, its constituents (macro and micro), existing guidelines for wastewater reuse, current treatment methods (from storage to disinfection) as well as related costs and environmental impacts. Moreover some successful examples from various countries around the world are examined. The current preferred treatments for GW use physical and biological/natural systems. Recently, chemical systems like coagulation, adsorption and advanced oxidation processes (AOPs) have been considered and have been successful for low to moderate strength GW. The presence of xenobiotic organic compounds (XOC), which are hazardous micropollutants in GW, is emphasised. Since conventional treatments are not efficient at removing XOC, it is recommended that future studies look at chemical treatment, especially AOPs that have been found to be successful at mineralising recalcitrant organic compounds in wastewater.

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Squire, Jeffrey N. T. « Biomedical Pollutants in the Urban Environment and Implications for Public Health : A Case Study ». ISRN Public Health 2013 (7 mai 2013) : 1–5. http://dx.doi.org/10.1155/2013/497490.

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This study investigated the management of biomedical pollutants in the Accra Metropolitan Area in Ghana, using a qualitative case study approach involving interviews, focus-group discussions, and observation techniques. A state of precariousness was found to characterize the management of biomedical pollutants in the study area, culminating in the magnification of risks to the environment and public health. There is neither a single sanitary landfill nor a properly functioning incineration system in the entire metropolis, and most of the healthcare facilities surveyed lack access to suitable treatment technologies. As a result, crude burning and indiscriminate dumping of infectious and toxic biomedical residues were found to be widespread. The crude burning of toxic biomedical pollutants was found to provide environmental pathways for carcinogenic substances. These include polynuclear aromatic hydrocarbons (PAHs), polychlorinated dibenzofurans (PCDFs), polychlorinated dibenzo-para-dioxins (PCDDs), polychlorinated biphenyls (PCBs), hydrogen, lead, mercury, cadmium, chlorobenzenes, particulate matter, and chlorophenols. The improper disposal of biomedical pollutants in open dumps and unsanitary landfills also carries a risk of providing environmental entry points for volatile organic compounds (VOCs), inorganic macrocomponents, heavy metals, and xenobiotic organic compounds.

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Micarelli, Alessandro, Andrea Cormano, Daniela Caccamo et Marco Alessandrini. « Olfactory-Related Quality of Life in Multiple Chemical Sensitivity : A Genetic-Acquired Factors Model ». International Journal of Molecular Sciences 21, n^o 1 (25 décembre 2019) : 156. http://dx.doi.org/10.3390/ijms21010156.

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Genetic polymorphisms as well as environmental exposures to chemical compounds, iatrogenic, psychological, and physical trauma may play a pathophysiological role in multiple chemical sensitivity (MCS) olfactory complaints, given that xenobiotic metabolism is influenced by sequence variations in genes of metabolizing enzymes. Thus, the aim of the present study was to depict—by means of multiple regression analysis—how different genetic conditions, grouped according to their function as well as clinical background and environmental exposure may interfere with those olfactory complaints referred by MCS patients. Therefore, MCS patients after gene polymorphism sequencing, the olfactory-related quality of life score—calculated by means of the Questionnaire of Olfactory Disorder in forty-six MCS patients—have been found to significantly rely on the phase I and II enzymes score and exposure to previous compounds and surgical treatments. The present work—implementing for the first time a genetic-acquired factors model on a regression analysis—further reinforces those theories, positing MCS as a complex, multifactorial, disease in which the genetic risk related to phase I and II enzymes involved in xenobiotic detoxification, olfactory, and neurodegenerative diseases play a necessary, but probably not sufficient role, along the pathophysiological route of the disease.

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Wang, Shaoyun, Xiaozhu Sun, Shuo An, Fang Sang, Yunli Zhao et Zhiguo Yu. « High-Throughput Identification of Organic Compounds from Polygoni Multiflori Radix Praeparata (Zhiheshouwu) by UHPLC-Q-Exactive Orbitrap-MS ». Molecules 26, n^o 13 (29 juin 2021) : 3977. http://dx.doi.org/10.3390/molecules26133977.

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Polygoni Multiflori Radix Praeparata (PMRP), as the processed product of tuberous roots of Polygonum multiflorum Thunb., is one of the most famous traditional Chinese medicines, with a long history. However, in recent years, liver adverse reactions linked to PMRP have been frequently reported. Our work attempted to investigate the chemical constituents of PMRP for clinical research and safe medication. In this study, an effective and rapid method was established to separate and characterize the constituents in PMRP by combining ultra-high performance liquid chromatography with hybrid quadrupole-orbitrap mass spectrometry (UHPLC-Q-Exactive Orbitrap-MS). Based on the accurate mass measurements for molecular and characteristic fragment ions, a total of 103 compounds, including 24 anthraquinones, 21 stilbenes, 15 phenolic acids, 14 flavones, and 29 other compounds were identified or tentatively characterized. Forty-eight compounds were tentatively characterized from PMRP for the first time, and their fragmentation behaviors were summarized. There were 101 components in PMRP ethanol extract (PMRPE) and 91 components in PMRP water extract (PMRPW). Simultaneously, the peak areas of several potential xenobiotic components were compared in the detection, which showed that PMRPE has a higher content of anthraquinones and stilbenes. The obtained results can be used in pharmacological and toxicological research and provided useful information for further in vitro and in vivo studies.

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Kim, Hyun Jung, Soon-Ho Yim, Fubo Han, Bok Yun Kang, Hyun Jin Choi, Da-Woon Jung, Darren R. Williams, Kirk R. Gustafson, Edward J. Kennelly et Ik-Soo Lee. « Biotransformed Metabolites of the Hop Prenylflavanone Isoxanthohumol ». Molecules 24, n^o 3 (22 janvier 2019) : 394. http://dx.doi.org/10.3390/molecules24030394.

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A metabolic conversion study on microbes is known as one of the most useful tools to predict the xenobiotic metabolism of organic compounds in mammalian systems. The microbial biotransformation of isoxanthohumol (1), a major hop prenylflavanone in beer, has resulted in the production of three diastereomeric pairs of oxygenated metabolites (2–7). The microbial metabolites of 1 were formed by epoxidation or hydroxylation of the prenyl group, and HPLC, NMR, and CD analyses revealed that all of the products were diastereomeric pairs composed of (2S)- and (2R)- isomers. The structures of these metabolic compounds were elucidated to be (2S,2”S)- and (2R,2”S)-4′-hydroxy-5-methoxy-7,8-(2,2-dimethyl-3-hydroxy-2,3-dihydro-4H-pyrano)-flavanones (2 and 3), (2S)- and (2R)-7,4′-dihydroxy-5-methoxy-8-(2,3-dihydroxy-3-methylbutyl)-flavanones (4 and 5) which were new oxygenated derivatives, along with (2R)- and (2S)-4′-hydroxy-5-methoxy-2”-(1-hydroxy-1-methylethyl)dihydrofuro[2,3-h]flavanones (6 and 7) on the basis of spectroscopic data. These results could contribute to understanding the metabolic fates of the major beer prenylflavanone isoxanthohumol that occur in mammalian system.

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López, R., A. Méndez-Serrano, F. Mercado, L. F. Oropeza et R. Montero Montoya. « Oxidative stress index in chronic exposure to volatile organic compounds and their relation with genetic polymorphisms of xenobiotic metabolism ». Toxicology Letters 259 (octobre 2016) : S129. http://dx.doi.org/10.1016/j.toxlet.2016.07.330.

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Rosenfeld, P. E., J. J. J. Clark, A. R. Hensley et I. H. Suffet. « The use of an odour wheel classification for the evaluation of human health risk criteria for compost facilities ». Water Science and Technology 55, n^o 5 (1 mars 2007) : 345–57. http://dx.doi.org/10.2166/wst.2007.197.

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Odorants are released during the decomposition of organic waste at compost treatment plants. Composting releases volatile organic chemicals (VOCs), including alcohols, aldehydes, volatile fatty acids, ammonia and other nitrogen compounds, xenobiotic solvents, and various sulphur compounds into the environment as categorised by a compost odor wheel. Each odorant possesses a characteristic odour signature – quality and threshold as well as a toxicity value. This paper presents data relating the human odour detection limit to human health threshold criteria developed by the National Institute for Occupational Safety and Health, Occupational Safety and Health Administration, the United States Environmental Protection Agency Region 9 and the World Health Organisation. This comparison indicates that: (1) the human odour threshold concentrations (OTC) for most compost odorants are far lower than their respective human health risk (regulatory) threshold values, (2) several compost odorants have OTC that are below some of their respective regulatory thresholds and above others (i.e. dimethyl amine, formic acid acetone, ethyl benzene and toluene) and (3) only the VOCs probably present as contaminants in the raw composting material have OTC greater than all of its regulatory thresholds (i.e. benzene). Benzene is the most hazardous VOC associated with composting and should be monitored.

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Costea, Teodora, Ariana Hudiță, Oana-Alina Ciolac, Bianca Gălățeanu, Octav Ginghină, Marieta Costache, Constanța Ganea et Maria-Magdalena Mocanu. « Chemoprevention of Colorectal Cancer by Dietary Compounds ». International Journal of Molecular Sciences 19, n^o 12 (28 novembre 2018) : 3787. http://dx.doi.org/10.3390/ijms19123787.

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Colorectal cancer is one of the leading causes of death, and the third most diagnosed type of cancer, worldwide. It is most common amongst men and women over 50 years old. Risk factors include smoking, alcohol, diet, physical inactivity, genetics, alterations in gut microbiota, and associated pathologies (diabetes, obesity, chronic inflammatory bowel diseases). This review will discuss, in detail, the chemopreventive properties of some dietary compounds (phenolic compounds, carotenoids, iridoids, nitrogen compounds, organosulfur compounds, phytosterols, essential oil compounds, polyunsaturated fatty acids and dietary fiber) against colorectal cancer. We present recent data, focusing on in vitro, laboratory animals and clinical trials with the previously mentioned compounds. The chemopreventive properties of the dietary compounds involve multiple molecular and biochemical mechanisms of action, such as inhibition of cell growth, inhibition of tumor initiation, inhibition of adhesion, migration and angiogenesis, apoptosis, interaction with gut microbiota, regulation of cellular signal transduction pathways and xenobiotic metabolizing enzymes, etc. Moreover, this review will also focus on the natural dietary compounds’ bioavailability, their synergistic protective effect, as well as the association with conventional therapy. Dietary natural compounds play a major role in colorectal chemoprevention and continuous research in this field is needed.

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Sykes, Destiny, Douglas H. Sweet, Simon Lowes, Sanjay K. Nigam, John B. Pritchard et David S. Miller. « Organic anion transport in choroid plexus from wild-type and organic anion transporter 3 (Slc22a8)-null mice ». American Journal of Physiology-Renal Physiology 286, n^o 5 (mai 2004) : F972—F978. http://dx.doi.org/10.1152/ajprenal.00356.2003.

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The choroid plexus actively transports endogenous, xenobiotic, and therapeutic compounds from cerebrospinal fluid to blood, thereby limiting their exposure to the central nervous system (CNS). Establishing the mechanisms responsible for this transport is critical to our understanding of basic choroid plexus physiology and will likely impact drug targeting to the CNS. We recently generated an organic anion transporter 3- (Oat3)-null mouse, which exhibited loss of PAH, estrone sulfate, and taurocholate transport in kidney and of fluorescein (FL) transport in choroid plexus. Here, we measured the uptake of four Oat3 substrates by choroid plexus from wild-type and Oat3-null mice to establish 1) the contribution of Oat3 to the apical uptake of each substrate and 2) the Na dependence of transport by Oat3 in the intact tissue. Mediated transport of PAH and FL was essentially abolished in tissue from Oat3-null mice. In contrast, only a 33% reduction in estrone sulfate uptake was observed in tissue from Oat3-null mice and, surprisingly, no reduction in taurocholate uptake could be detected. For PAH, FL, and estrone sulfate, all Oat3-mediated transport was Na dependent. However, estrone sulfate and taurocholate also exhibited additional mediated and Na-dependent components of uptake that were not attributed to Oat3, demonstrating the complexity of organic anion transport in this tissue and the need for further examination of expressed transporters and their energetics.

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Solé, Magali, Ines Müller, Marek J. Pecyna, Ingo Fetzer, Hauke Harms et Dietmar Schlosser. « Differential Regulation by Organic Compounds and Heavy Metals of Multiple Laccase Genes in the Aquatic Hyphomycete Clavariopsis aquatica ». Applied and Environmental Microbiology 78, n^o 13 (27 avril 2012) : 4732–39. http://dx.doi.org/10.1128/aem.00635-12.

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ABSTRACTTo advance the understanding of the molecular mechanisms controlling microbial activities involved in carbon cycling and mitigation of environmental pollution in freshwaters, the influence of heavy metals and natural as well as xenobiotic organic compounds on laccase gene expression was quantified using quantitative real-time PCR (qRT-PCR) in an exclusively aquatic fungus (the aquatic hyphomyceteClavariopsis aquatica) for the first time. Five putative laccase genes (lcc1tolcc5) identified inC. aquaticawere differentially expressed in response to the fungal growth stage and potential laccase inducers, with certain genes being upregulated by, e.g., the lignocellulose breakdown product vanillic acid, the endocrine disruptor technical nonylphenol, manganese, and zinc.lcc4is inducible by vanillic acid and most likely encodes an extracellular laccase already excreted during the trophophase of the organism, suggesting a function during fungal substrate colonization. Surprisingly, unlike many laccases of terrestrial fungi, none of theC. aquaticalaccase genes was found to be upregulated by copper. However, copper strongly increases extracellular laccase activity inC. aquatica, possibly due to stabilization of the copper-containing catalytic center of the enzyme. Copper was found to half-saturate laccase activity already at about 1.8 μM, in favor of a fungal adaptation to low copper concentrations of aquatic habitats.

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Matsuzaka, Yasunari, Takuomi Hosaka, Anna Ogaito, Kouichi Yoshinari et Yoshihiro Uesawa. « Prediction Model of Aryl Hydrocarbon Receptor Activation by a Novel QSAR Approach, DeepSnap–Deep Learning ». Molecules 25, n^o 6 (13 mars 2020) : 1317. http://dx.doi.org/10.3390/molecules25061317.

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The aryl hydrocarbon receptor (AhR) is a ligand-dependent transcription factor that senses environmental exogenous and endogenous ligands or xenobiotic chemicals. In particular, exposure of the liver to environmental metabolism-disrupting chemicals contributes to the development and propagation of steatosis and hepatotoxicity. However, the mechanisms for AhR-induced hepatotoxicity and tumor propagation in the liver remain to be revealed, due to the wide variety of AhR ligands. Recently, quantitative structure–activity relationship (QSAR) analysis using deep neural network (DNN) has shown superior performance for the prediction of chemical compounds. Therefore, this study proposes a novel QSAR analysis using deep learning (DL), called the DeepSnap–DL method, to construct prediction models of chemical activation of AhR. Compared with conventional machine learning (ML) techniques, such as the random forest, XGBoost, LightGBM, and CatBoost, the proposed method achieves high-performance prediction of AhR activation. Thus, the DeepSnap–DL method may be considered a useful tool for achieving high-throughput in silico evaluation of AhR-induced hepatotoxicity.

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Lønborg, Michael J., Peter Engesgaard, Poul L. Bjerg et Dan Rosbjerg. « A steady state redox zone approach for modeling the transport and degradation of xenobiotic organic compounds from a landfill site ». Journal of Contaminant Hydrology 87, n^o 3-4 (octobre 2006) : 191–210. http://dx.doi.org/10.1016/j.jconhyd.2006.05.004.

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Watanabe, Y., S. Okabe, K. Hirata et S. Masuda. « Simultaneous removal of organic materials and nitrogen by micro-aerobic biofilms ». Water Science and Technology 31, n^o 1 (1 janvier 1995) : 195–203. http://dx.doi.org/10.2166/wst.1995.0044.

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Simultaneous nitrification with denitrification was investigated using a single rotating biological contactor (RBC). The authors proposed two means to achieve simultaneous nitrification with denitrification in the single reactor: (1) to control oxygen transfer rate by reducing oxygen partial pressure (P02) in the air phase and (2) to develop a combined partially (aerobic) and fully (anaerobic) submerged RBC (CPFSR) reactor. For the former experiment, the maximum denitrification efficiency of 90 % was obtained at C:N ratio=6 and P02=0.10 atm. Moreover, heterotrophs, NH4- and NO2-oxidizers, and denitrifiers were distributed throughout the biofilm, suggesting that nitrification and denitrification can occur wheresoever the local environment meets their growth conditions. For the latter experiment, effects of type of organic matter and influent carbon:nitrogen ratio (C:N ratio) on the efficiency of simultaneous nitrification with denitrification were investigated using the CPFSR reactor. Acetate, ethylene-glycol, phenol, and poly-vinyl-alcohol (PVA) were used as carbon sources for denitrification. An excellent nitrification efficiency was obtained for all experimental runs and all organic substrates could be degraded and used for denitrification, indicating a great potential for simultaneous removals of nitrogen and xenobiotic compounds by the CPFSR reactor.

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Baulig, Augustin, Michèle Garlatti, Véronique Bonvallot, Alexandre Marchand, Robert Barouki, Francelyne Marano et Armelle Baeza-Squiban. « Involvement of reactive oxygen species in the metabolic pathways triggered by diesel exhaust particles in human airway epithelial cells ». American Journal of Physiology-Lung Cellular and Molecular Physiology 285, n^o 3 (septembre 2003) : L671—L679. http://dx.doi.org/10.1152/ajplung.00419.2002.

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Diesel exhaust particles (DEP) induce a proinflammatory response in human bronchial epithelial cells (16HBE) characterized by the release of proinflammatory cytokines after activation of transduction pathways involving MAPK and the transcription factor NF-κB. Because cellular effects induced by DEP are prevented by antioxidants, they could be mediated by reactive oxygen species (ROS). Using fluorescent probes, we detected ROS production in bronchial and nasal epithelial cells exposed to native DEP, organic extracts of DEP (OE-DEP), or several polyaromatic hydrocarbons. Carbon black particles mimicking the inorganic part of DEP did not increase ROS production. DEP and OE-DEP also induced the expression of genes for phase I [cytochrome P-450 1A1 (CYP1A1)] and phase II [NADPH quinone oxidoreductase-1 (NQO-1)] xenobiotic metabolization enzymes, suggesting that DEP-adsorbed organic compounds become bioavailable, activate transcription, and are metabolized since the CYP1A1 enzymatic activity is increased. Because NQO-1 gene induction is reduced by antioxidants, it could be related to the ROS generated by DEP, most likely through the activation of the stress-sensitive Nrf2 transcription factor. Indeed, DEP induced the translocation of Nrf2 to the nucleus and increased protein nuclear binding to the antioxidant responsive element. In conclusion, we show that DEP-organic compounds generate an oxidative stress, activate the Nrf2 transcription factor, and increase the expression of genes for phase I and II metabolization enzymes.

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Gugliandolo, Agnese, Placido Bramanti et Emanuela Mazzon. « Activation of Nrf2 by Natural Bioactive Compounds : A Promising Approach for Stroke ? » International Journal of Molecular Sciences 21, n^o 14 (10 juillet 2020) : 4875. http://dx.doi.org/10.3390/ijms21144875.

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Stroke represents one of the main causes of disability and death worldwide. The pathological subtypes of stroke are ischemic stroke, the most frequent, and hemorrhagic stroke. Nrf2 is a transcription factor that regulates redox homeostasis. In stress conditions, Nrf2 translocates inside the nucleus and induces the transcription of enzymes involved in counteracting oxidative stress, endobiotic and xenobiotic metabolism, regulators of inflammation, and others. Different natural compounds, including food and plant-derived components, were shown to be able to activate Nrf2, mediating an antioxidant response. Some of these compounds were tested in stroke experimental models showing several beneficial actions. In this review, we focused on the studies that evidenced the positive effects of natural bioactive compounds in stroke experimental models through the activation of Nrf2 pathway. Interestingly, different natural compounds can activate Nrf2 through multiple pathways, inducing a strong antioxidant response associated with the beneficial effects against stroke. According to several studies, the combination of different bioactive compounds can lead to a better neuroprotection. In conclusion, natural bioactive compounds may represent new therapeutic strategies against stroke.

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Kaiser, Lars, Helga Weinschrott, Isabel Quint, Markus Blaess, René Csuk, Manfred Jung, Matthias Kohl et Hans-Peter Deigner. « Metabolite Patterns in Human Myeloid Hematopoiesis Result from Lineage-Dependent Active Metabolic Pathways ». International Journal of Molecular Sciences 21, n^o 17 (24 août 2020) : 6092. http://dx.doi.org/10.3390/ijms21176092.

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Assessment of hematotoxicity from environmental or xenobiotic compounds is of notable interest and is frequently assessed via the colony forming unit (CFU) assay. Identification of the mode of action of single compounds is of further interest, as this often enables transfer of results across different tissues and compounds. Metabolomics displays one promising approach for such identification, nevertheless, suitability with current protocols is restricted. Here, we combined a hematopoietic stem and progenitor cell (HSPC) expansion approach with distinct lineage differentiations, resulting in formation of erythrocytes, dendritic cells and neutrophils. We examined the unique combination of pathway activity in glycolysis, glutaminolysis, polyamine synthesis, fatty acid oxidation and synthesis, as well as glycerophospholipid and sphingolipid metabolism. We further assessed their interconnections and essentialness for each lineage formation. By this, we provide further insights into active metabolic pathways during the differentiation of HSPC into different lineages, enabling profound understanding of possible metabolic changes in each lineage caused by exogenous compounds.

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Seliger, Jan, Serhat Cicek, Lydia Witt, Hans-Jörg Martin, Edmund Maser et Jan Hintzpeter. « Selective Inhibition of Human AKR1B10 by n-Humulone, Adhumulone and Cohumulone Isolated from Humulus lupulus Extract ». Molecules 23, n^o 11 (21 novembre 2018) : 3041. http://dx.doi.org/10.3390/molecules23113041.

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Hop-derived compounds have been subjected to numerous biomedical studies investigating their impact on a wide range of pathologies. Isomerised bitter acids (isoadhumulone, isocohumulone and isohumulone) from hops, used in the brewing process of beer, are known to inhibit members of the aldo-keto-reductase superfamily. Aldo-keto-reductase 1B10 (AKR1B10) is upregulated in various types of cancer and has been reported to promote carcinogenesis. Inhibition of AKR1B10 appears to be an attractive means to specifically treat RAS-dependent malignancies. However, the closely related reductases AKR1A1 and AKR1B1, which fulfil important roles in the detoxification of endogenous and xenobiotic carbonyl compounds oftentimes crossreact with inhibitors designed to target AKR1B10. Accordingly, there is an ongoing search for selective AKR1B10 inhibitors that do not interact with endogeneous AKR1A1 and AKR1B1-driven detoxification systems. In this study, unisomerised α-acids (adhumulone, cohumulone and n-humulone) were separated and tested for their inhibitory potential on AKR1A1, AKR1B1 and AKR1B10. Also AKR1B10-mediated farnesal reduction was effectively inhibited by α-acid congeners with Ki-values ranging from 16.79 ± 1.33 µM (adhumulone) to 3.94 ± 0.33 µM (n-humulone). Overall, α-acids showed a strong inhibition with selectivity (115–137 fold) for AKR1B10. The results presented herein characterise hop-derived α-acids as a promising basis for the development of novel and selective AKR1B10-inhibitors.

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Taylor-Wells, Jennina, et David Meredith. « The Signature Sequence Region of the Human Drug Transporter Organic Anion Transporting Polypeptide 1B1 Is Important for Protein Surface Expression ». Journal of Drug Delivery 2014 (9 octobre 2014) : 1–10. http://dx.doi.org/10.1155/2014/129849.

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The organic anion transporting polypeptides (OATPs) encompass a family of membrane transport proteins responsible for the uptake of xenobiotic compounds. Human organic anion transporting polypeptide 1B1 (OATP1B1) mediates the uptake of clinically relevant compounds such as statins and chemotherapeutic agents into hepatocytes, playing an important role in drug delivery and detoxification. The OATPs have a putative 12-transmembrane domain topology and a highly conserved signature sequence (human OATP1B1: DSRWVGAWWLNFL), spanning the extracellular loop 3/TM6 boundary. The presence of three conserved tryptophan residues at the TM interface suggests a structural role for the sequence. This was investigated by site-directed mutagenesis of selected amino acids within the sequence D251E, W254F, W258/259F, and N261A. Transport was measured using the substrate estrone-3-sulfate and surface expression detected by luminometry and confocal microscopy, facilitated by an extracellular FLAG epitope. Uptake of estrone-3-sulfate and the surface expression of D251E, W254F, and W258/259F were both significantly reduced from the wild type OATP1B1-FLAG in transfected HEK293T cells. Confocal microscopy revealed that protein was produced but was retained intracellularly. The uptake and expression of N261A were not significantly different. The reduction in surface expression and intracellular protein retention indicates a structural and/or membrane localization role for these signature sequence residues in the human drug transporter OATP1B1.

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Preiss, A., E. Berger-Preiss, M. Elend, S. Gerling, S. Kühn et S. Schuchardt. « A new analytical approach for the comprehensive characterization of polar xenobiotic organic compounds downgradient of old municipal solid waste (MSW) landfills ». Analytical and Bioanalytical Chemistry 403, n^o 9 (12 avril 2012) : 2553–61. http://dx.doi.org/10.1007/s00216-012-5941-7.

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Deksissa, Tolessa, Dirk De Pauw et Peter A. Vanrolleghem. « DYNAMIC IN-STREAM FATE MODELING OF XENOBIOTIC ORGANIC COMPOUNDS : A CASE STUDY OF LINEAR ALKYLBENZENE SULFONATES IN THE LAMBRO RIVER, ITALY ». Environmental Toxicology and Chemistry 23, n^o 9 (2004) : 2267. http://dx.doi.org/10.1897/03-466.

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Smets, Barth F., Timothy G. Ellis, Stephanie Brau, Richard W. Sanders et C. P. Leslie Grady. « Quantification of the kinetic differences between communities isolated from completely mixed activated sludge systems operated with or without a selector using a novel respirometric method ». Water Science and Technology 30, n^o 11 (1 décembre 1994) : 255–61. http://dx.doi.org/10.2166/wst.1994.0567.

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This study quantified the kinetic differences in microbial communities isolated from completely mixed activated sludge (CMAS) systems that were operated either with or without an aerobic selector preceding the main reactor. A new respirometric method was employed that allowed the determination of biodegradation kinetics from single oxygen consumption curves, thereby minimizing physiological changes to the examined communities during the assay. Results indicated that increased values for Ks and μmax for acetate, phenol, and 4-chlorophenol degradation were measured in the CMAS system operated with a selector. The biomass yields on acetate, phenol, and 4-chlorophenol were very similar in both systems. These findings indicate that the operation of CMAS systems with aerobic selectors may result in the selection for degrading populations with higher Ks and μmax values for both biogenic and xenobiotic organic compounds, and that substrate storage in the selector only partially contributes to increased substrate removal rates.

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Ahmad, R., et A. Srivastava. « Inhibition of Filarial Glutathione-S-transferase by various classes of compounds and their evaluation as novel antifilarial agents ». Helminthologia 45, n^o 3 (1 septembre 2008) : 114–20. http://dx.doi.org/10.2478/s11687-008-0022-3.

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AbstractGlutathione S-transferase(s); GST(s) (E.C. 2.5.1.18) are a large family of multifunctional dimeric enzymes that conjugate reduced glutathione to electrophilic centres in hydrophobic organic compounds. GST(s) represent the major class of detoxifying enzymes from parasitic helminths. The GST enzymatic activity has been described in the adult and larval stages of helminths. Several forms and isoforms of the enzyme have been purified and GST genes have also been isolated and expressed as recombinant proteins. The helminth GST(s) participate in detoxification of lipid hydroperoxides and cytotoxic carbonyl compounds produced by oxygen-reactive intermediates (ORIs). The ORIs can come from the endogenous parasite metabolism or from the host immune system. The helminth GST(s) are able to conjugate glutathione to xenobiotic compounds or to bind to the anthelminth drugs. GST is usually found to be localized near to host-parasite interface. This enzyme has been identified as a potentially vulnerable target in immunotherapy and chemotherapy of parasitic diseases. The most effective drug candidates are those based on inhibitors of GST. In the present study, purified GST from cytosolic fraction of bovine filarial worms Setaria cervi was inhibited in a concentration dependent fashion by various compounds such as hemin, ethacrynic acid, S-hexylglutathione, quercetin, cibacron blue, lithocholate sulfate and ellagic acid. Cytosolic GST was inhibited to varying degrees by each inhibitor. In this context, the possible physiological significance of the observed results has been discussed.

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VanWert, Adam L., Rachel M. Bailey et Douglas H. Sweet. « Organic anion transporter 3 (Oat3/Slc22a8) knockout mice exhibit altered clearance and distribution of penicillin G ». American Journal of Physiology-Renal Physiology 293, n^o 4 (octobre 2007) : F1332—F1341. http://dx.doi.org/10.1152/ajprenal.00319.2007.

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The interaction of renal basolateral organic anion transporter 3 (Oat3) with commonly used pharmacotherapeutics (e.g., NSAIDs, β-lactams, and methotrexate) has been studied extensively in vitro. However, the in vivo role of Oat3 in drug disposition, in the context of other transporters, glomerular filtration, and metabolism, has not been established. Moreover, recent investigations have identified inactive human OAT3 polymorphisms. Therefore, this investigation was designed to elucidate the in vivo role of Oat3 in the disposition of penicillin G and prototypical substrates using an Oat3 knockout mouse model. Oat3 deletion resulted in a doubling of penicillin's half-life ( P < 0.05) and a reduced volume of distribution ( P < 0.01), together yielding a plasma clearance that was one-half ( P < 0.05, males) to one-third ( P < 0.001, females) of that in wild-type mice. Inhibition of Oat3 abolished the differences in penicillin G elimination between genotypes. Hepatic accumulation of penicillin was 2.3 times higher in male knockouts ( P < 0.05) and 3.7 times higher in female knockouts ( P < 0.001). Female knockouts also exhibited impaired estrone-3-sulfate clearance. Oat3 deletion did not impact p-aminohippurate elimination, providing correlative evidence to studies in Oat1 knockout mice that suggest Oat1 governs tubular uptake of p-aminohippurate. Collectively, these findings are the first to indicate that functional Oat3 is necessary for proper elimination of xenobiotic and endogenous compounds in vivo. Thus Oat3 plays a distinct role in determining the efficacy and toxicity of drugs. Dysfunctional human OAT3 polymorphisms or instances of polypharmacy involving OAT3 substrates may result in altered systemic accumulation of β-lactams and other clinically relevant compounds.

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Ellis, Timothy G., Barth F. Smets, Benjamin S. Magbanua et C. P. Leslie Grady. « Changes in measured biodegradation kinetics during the long-term operation of completely mixed activated sludge (CMAS) bioreactors ». Water Science and Technology 34, n^o 5-6 (1 septembre 1996) : 35–42. http://dx.doi.org/10.2166/wst.1996.0532.

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Two completely mixed activated sludge (CMAS) bioreactors, one with an aerobic selector and one without, were operated for approximately twelve and sixteen months, respectively. Extant biodegradation kinetics for several compounds were periodically tested using a batch respirometric procedure. Kinetic parameters from the CMAS unit without a selector showed considerable variability (standard deviation of ± 50%) even though it was operated at steady state (i.e. constant HRT, SRT, organic loading, etc.) for the duration of the study. At first, there was a large discrepancy between the kinetic parameters of the two bioreactors. Phenol and 4-chlorophenol were biodegraded according to Monod kinetics in the selector system and Andrews (inhibitory) kinetics in the non-selector system, and the μ^ and KS values were significantly greater in the selector system. The kinetic parameter values of the two systems converged, however, when the xenobiotic compounds were no longer fed to the selector in that system but were fed to the main bioreactor. After this switch, phenol and 4-chlorophenol followed inhibitory kinetics in both systems. The lack of inhibition when phenol and 4-chlorophenol were fed to the selector suggests that, contrary to conventional wisdom, bioreactors which have a concentration gradient (e.g. plug flow, sequencing batch, and tanks in series bioreactors) may be more resistant to inhibition.

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