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Carol A Marchant, Edward M Rosser, Jonathan D Vessey
The application of biotransformation dictionaries derived by expert evaluation of known metabolic pathways represents one approach to the prediction of both phase I and phase II xenobiotic metabolites. The ranking of metabolites generated by such dictionaries has previously been achieved through the use of qualitative reasoning rules and quantitative probability values. Using the biotransformation dictionary available in the Meteor expert system, we show that metabolite over-prediction by both of these methods can be reduced by the adoption of a k-nearest neighbours methodology in which the likelihood of a predicted biotransformation is determined based on comparison of a query chemical with structurally-similar substrates with known experimental metabolic data which activate the same biotransformation...
October 25, 2016: Molecular Informatics
June Ho Shin, Mikel D Haggadone, John B Sunwoo
The Distal-less (Dlx) homeobox transcription factors (TFs) play a prominent role in regulating multiple facets of vertebrate biology. Though widely studied as mediators of tissue development, recent work has uncovered a role for this TF family in modulating the vertebrate hematopoietic compartment. Pertinent to our study, murine Dlx1-3 are expressed in an innate lymphocyte population known as natural killer (NK) cells, and they are implicated to assume a functional role in the NK cell maturation pathway. However, Dlx target genes are poorly understood...
September 2016: Biochemistry and Biophysics Reports
Chang Chen, Ariane Wohlfarth, Hui Xu, Dan Su, Xin Wang, Hongliang Jiang, Yulin Feng, Mingshe Zhu
A novel analytical workflow was developed and applied for the detection and identification of unknown xenobiotics in biological samples. High-resolution mass spectrometry (HRMS)-based data-independent MS(E) acquisition was employed to record full scan MS and fragment spectral datasets of test and control samples. Then, an untargeted data-mining technique, background subtraction, was utilized to find xenobiotics present only in test samples. Structural elucidation of the detected xenobiotics was accomplished by database search, spectral interpretation, and/or comparison with reference standards...
November 9, 2016: Analytica Chimica Acta
Jing Li, Aping Niu, Chun-Jiao Lu, Jing-Hui Zhang, Muhammad Junaid, Phyllis R Strauss, Ping Xiao, Xiao Wang, Yi-Wei Ren, De-Sheng Pei
Landfill leachate (LL) is harmful to aquatic environment because it contains high concentrations of dissolved organic matter, inorganic components, heavy metals, and other xenobiotics. Thus, the remediation of LL is crucial for environmental conservation. Here, a potential application of the forward osmosis (FO) filtration process with ammonium bicarbonate (NH4HCO3) as a draw solution (DS) was investigated to remediate membrane bioreactor-treated LL (M-LL). After the leachate treatment, the toxicity and removal efficiencies of polycyclic aromatic hydrocarbons (PAHs) were evaluated using zebrafish and cultured human cells...
October 21, 2016: Chemosphere
Hyun-Jung Sung, Kyung-Hyun Kim, Young-In Maeng, Kwan-Kyu Park
No abstract text is available yet for this article.
February 2016: Pathology
Hans-Uwe Dahms, Eun-Ji Won, Hui-Su Kim, Jeonghoon Han, Heum Gi Park, Sami Souissi, Sheikh Raisuddin, Jae-Seong Lee
Aquatic invertebrates contribute significantly to environmental impact assessment of contaminants in aquatic ecosystems. Much effort has been made to identify viable and ecologically relevant invertebrate test organisms to meet rigorous regulatory requirements. Copepods, which are ecologically important and widely distributed in aquatic organisms, offer a huge opportunity as test organisms for aquatic toxicity testing. They have a major role not only in the transfer of energy in aquatic food chains, but also as a medium of transfer of aquatic pollutants across the tropic levels...
October 14, 2016: Aquatic Toxicology
Norimitsu Shirai, Frank J Geoly, Walter F Bobrowski, Carlin Okerberg
Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies in cells exposed to xenobiotics. Demonstration of the lamellar bodies by transmission electron microscopy (TEM) is the hallmark for a definitive diagnosis of phospholipidosis. However, the preparation of tissue samples for TEM and their ultrastructural evaluation are technically challenging and time consuming. Paraphenylenediamine (PPD) is essentially a fat stain, and the staining mechanism is based upon the osmication of unsaturated lipids...
October 21, 2016: Toxicologic Pathology
Francisco X Nascimento, Margarida Espada, Pedro Barbosa, Márcio J Rossi, Cláudia S L Vicente, Manuel Mota
The aim of this study is to understand the biological role of Serratia quinivorans BXF1, a bacterium commonly found associated with Bursaphelenchus xylophilus, the plant parasitic nematode responsible for pine wilt disease. Therefore, we studied strain BXF1 effect in pine wilt disease. We found that strain BXF1 promoted in vitro nematode reproduction. Moreover, the presence of bacteria led to the absence of nematode chitinase gene (Bxcht-1) expression, suggesting an effect for bacterial chitinase in nematode reproduction...
October 21, 2016: Environmental Microbiology
Jennifer Hennen, Brunhilde Blömeke
In vitro approaches address key steps of chemical-induced skin sensitization but there is uncertainty how keratinocytes, which play a crucial role not only regarding xenobiotic metabolism but also skin inflammation, impact on chemicals' potential and potency of dendritic cell activation. We investigated these aspects by coculturing THP-1 cells, as surrogate dendritic cells, with HaCaT keratinocytes. We tested our HaCaT/THP-1 model with a set of 14 sensitizers, containing 7 prohaptens, and 10 non-sensitizers...
October 21, 2016: ALTEX
Paula Viviani, Adrian Lifschitz, Jorge García, María Laura Maté, Miguel Angel Quiroga, Carlos Lanusse, Guillermo Virkel
1. Precision-cut liver slices (PCLS) from food-producing animals have not been extensively used to study xenobiotic metabolism, and thus information on this field of research is sparse. 2. The aims of the present work were to further validate the technique of production and culture of bovine PCLS and to characterize the metabolic interaction between the anthelmintic albendazole (ABZ) and the flavin-monooxygenase (FMO) inhibitor methimazole (MTZ). 3. Nine (9) steers were used as donors. PCLS were produced and incubated under two methods, a dynamic organ culture (DOC) incubator and a well-plate (WP) system...
October 21, 2016: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
Christoph Funk, Adrian Roth
Drug-induced liver injury (DILI) is a major concern for drug developers, regulators and clinicians. It is triggered by drug and xenobiotic insults leading to liver impairment or damage, in the worst-case liver failure. In contrast to acute "intrinsic" hepatotoxicity, DILI typically manifests in a very small subset of the population under treatment with no clear dose relationship and inconsistent temporal patterns and is therefore termed an idiosyncratic event. Involved are multifactorial, compound-dependent mechanisms and host-specific factors, making the prediction in preclinical test systems very challenging...
October 20, 2016: Archives of Toxicology
Nicola Stefano Fracchiolla, Claudio Annaloro, Francesca Guidotti, Bruno Fattizzo, Agostino Cortelezzi
Dioxin exposure and its effect on hematopoiesis and cancer have been largely investigated in both human and non-human settings. Here we systematically reviewed literature to address the question of what we know about TCDD biology and exposure. Most effects are due to TCDD interaction with a receptor of xenobiotics called AHR, which is ubiquitously represented and also works on hematopoietic myeloid and lymphoid stem cells, inducing proliferation and stem cell release from bone marrow to peripheral circulation...
October 17, 2016: Toxicology
Fadia S Youssef, Mohamed L Ashour, Mansour Sobeh, Hesham A El-Beshbishy, Abdel Nasser Singab, Michael Wink
BACKGROUND: The Australian plant Eremophila maculata F. Muell (Scrophulariaceae) is cultivated worldwide as an ornamental plant. PURPOSE: This study was designed to assess the antioxidant and hepatoprotective activities of a methanol extract from E. maculata leaves (EMM) both in vitro and in vivo (rats) experiments. Detailed phytochemical study was done on the extract followed by molecular docking experiments on TNF-α ascertain the efficacy of the isolated compounds...
November 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Ivo Šafařík, Zdenka Maděrová, Kristýna Pospíšková, Hans-Peter Schmidt, Eva Baldíková, Jan Filip, Michal Křížek, Ondřej Malina, Mirka Šafaříková
Large amounts of biochar are produced worldwide for potential agricultural applications. However, this material can also be used as an efficient biosorbent for xenobiotics removal. In this work, biochar was magnetically modified using microwave-synthesized magnetic iron oxide particles. This new type of a magnetically responsive biocomposite material can be easily separated by means of strong permanent magnets. Magnetic biochar has been used as an inexpensive magnetic adsorbent for the removal of water-soluble dyes...
October 2016: Water Science and Technology: a Journal of the International Association on Water Pollution Research
Deepak Kotiya, Bharti Jaiswal, Sampa Ghose, Rachna Kaul, Kasturi Datta, Rakesh K Tyagi
The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity...
2016: PloS One
Katherine A Dunn, Jessica Moore-Connors, Brad MacIntyre, Andrew Stadnyk, Nikhil A Thomas, Angela Noble, Gamal Mahdi, Mohsin Rashid, Anthony R Otley, Joseph P Bielawski, Johan Van Limbergen
BACKGROUND: Exclusive enteral nutrition (EEN) is a first-line therapy in pediatric Crohn's disease (CD) thought to induce remission through changes in the gut microbiome. With microbiome assessment largely focused on microbial taxonomy and diversity, it remains unclear to what extent EEN induces functional changes that thereby contribute to its therapeutic effect. METHODS: Fecal samples were collected from 15 pediatric CD patients prior to and after EEN treatment, as well as from 5 healthy controls...
November 2016: Inflammatory Bowel Diseases
Aaron P Roberts, Matthew M Alloy, James T Oris
Solar radiation is a vital component of ecosystem function. However, sunlight can also interact with certain xenobiotic compounds in a phenomenon known as photo-induced, photo-enhanced, photo-activated, or photo-toxicity. This phenomenon broadly refers to an interaction between a chemical and sunlight resulting in increased toxicity. Because most aquatic ecosystems receive some amount of sunlight, co-exposure to xenobiotic chemicals and solar radiation is likely to occur in the environment, and photo-induced toxicity may be an important factor impacting aquatic ecosystems...
October 15, 2016: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
Vera Erdman, Ilsia Tuktarova, Timur Nasibullin, Ianina Timasheva, Olga Mustafina
OBJECTIVE: Physiological and biochemical changes during aging alter drug metabolism. Drug intake is increased with age because of cumulative morbidity, in particular, high prevalence of cardiovascular diseases. Antihypertensive medications are the most commonly used drugs. Individual drug sensitivity or resistance may be influenced by the variance of the "pharmacological response" genes.Our purpose was to search for the polymorphic variants of "pharmacological response" genes associated with survival in different age periods...
September 2016: Journal of Hypertension
Catherine A Picut, George A Parker
Toxicologic pathologists must evaluate tissues of immature animals from a number of types of nonclinical toxicity studies. The pathologist who is familiar with normal postnatal organ development is in a better position to appropriately detect and differentiate between abnormal, delayed, or precocious development. Vacuolation and apoptosis in multiple tissue types are normal components of development that could influence the interpretation of some tissues. Unique postnatal features such as the germal matrix in the brain, gonocytes in the testes, and saccules in the lung may complicate the histopathological evaluation...
October 17, 2016: Toxicologic Pathology
Katharina Kaufmann, Peter Dohmen
BACKGROUND: Literature data indicate that terrestrial life stages of amphibians may be more sensitive to xenobiotics than birds or mammals. It is hypothesized that dermal exposure could potentially be a significant route of exposure for amphibians, as there is evidence that their skin is more permeable than the skin of other vertebrate species. Thus, higher amounts of xenobiotics might enter systemic circulation by dermal uptake resulting in adverse effects. Heretofore, no guidelines exist to investigate dermal toxicity of chemicals to amphibians...
2016: Environmental Sciences Europe
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