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https://www.readbyqxmd.com/read/29458109/modulation-of-cyp1a1-metabolism-from-adverse-health-effects-to-chemoprevention-and-therapeutic-options
#1
Melina Mescher, Thomas Haarmann-Stemmann
The human cytochrome P450 (CYP) 1A1 gene encodes a monooxygenase that metabolizes multiple exogenous and endogenous substrates. CYP1A1 has become infamous for its oxidative metabolism of benzo[a]pyrene and related polycyclic aromatic hydrocarbons, converting these chemicals into very potent human carcinogens. CYP1A1 expression is mainly controlled by the aryl hydrocarbon receptor (AHR), a transcription factor whose activation is induced by binding of persistent organic pollutants, including polycyclic aromatic hydrocarbons and dioxins...
February 16, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29453911/induction-of-xenobiotic-metabolizing-enzymes-in-hepatocytes-by-beta-naphthoflavone-time-dependent-changes-in-activities-protein-and-mrna-levels
#2
Kateřina Lněničková, Lenka Skálová, Lucie Stuchlíková, Barbora Szotáková, Petra Matoušková
In the present study, time-dependency of the induction effect of a selective inducer on the activity, protein and mRNA levels of cytochromes P450 1A1/2 (CYP1A1/2), NAD(P)H:quinone oxidoreductase 1 (NQO1) and glutathione S-transferases (GSTA), in primary culture of rat hepatocytes was tested and evaluated. To show the differences in responses of tested enzymes, the common aryl hydrocarbon receptor (AhR) ligand agonist, beta-naphthoflavone (BNF), was used. Induction of CYP1A1/2 by BNF was detected at all time intervals and at all levels (i...
March 1, 2018: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29451034/cytochrome-p450-in-the-central-nervous-system-as-a-therapeutic-target-in-neurodegenerative-diseases
#3
Cynthia Navarro-Mabarak, Rafael Camacho-Carranza, Jesús Javier Espinosa-Aguirre
Cytochromes P450 (CYPs) constitute a family of enzymes that can be found in the endoplasmic reticulum (ER), mitochondria or the cell surface of the cells. CYPs are characterized by carrying out the oxidation of organic compounds and they are mainly recognized as mediators of the biotransformation of xenobiotics to polar hydrophilic metabolites that can be eliminated from the organism. However, these enzymes play a key role in many other physiological processes, being involved in diverse indispensable metabolic pathways since they metabolize many endogenous substrates...
February 16, 2018: Drug Metabolism Reviews
https://www.readbyqxmd.com/read/29447380/sirtuins-in-gamete-biology-and-reproductive-physiology-emerging-roles-and-therapeutic-potential-in-female-and-male-infertility
#4
Carla Tatone, Giovanna Di Emidio, Arcangelo Barbonetti, Gaspare Carta, Alberto M Luciano, Stefano Falone, Fernanda Amicarelli
BACKGROUND: Sirtuins (SIRT1-7) are a family of NAD+-dependent deacetylases that catalyze post-translational modifications of proteins. Together, they respond to metabolic challenges, inflammatory signals or hypoxic/oxidative stress, and are associated with aging and longevity. The role of Sirtuins in the regulation of fertility emerged in 2003 when a defective reproductive phenotype was observed in SIRT1-null mice. Although studies on Sirtuins in reproductive biology have been increasing in the last years, a recent comprehensive update on this issue is still lacking...
February 13, 2018: Human Reproduction Update
https://www.readbyqxmd.com/read/29447216/genome-mining-of-streptomyces-scabrisporus-nf3-reveals-symbiotic-features-including-genes-related-to-plant-interactions
#5
Corina Diana Ceapă, Melissa Vázquez-Hernández, Stefany Daniela Rodríguez-Luna, Angélica Patricia Cruz Vázquez, Verónica Jiménez Suárez, Romina Rodríguez-Sanoja, Elena R Alvarez-Buylla, Sergio Sánchez
Endophytic bacteria are wide-spread and associated with plant physiological benefits, yet their genomes and secondary metabolites remain largely unidentified. In this study, we explored the genome of the endophyte Streptomyces scabrisporus NF3 for discovery of potential novel molecules as well as genes and metabolites involved in host interactions. The complete genomes of seven Streptomyces and three other more distantly related bacteria were used to define the functional landscape of this unique microbe. The S...
2018: PloS One
https://www.readbyqxmd.com/read/29447178/joint-ancestry-and-association-test-indicate-two-distinct-pathogenic-pathways-involved-in-classical-dengue-fever-and-dengue-shock-syndrome
#6
Marisa Oliveira, Worachart Lert-Itthiporn, Bruno Cavadas, Verónica Fernandes, Ampaiwan Chuansumrit, Orlando Anunciação, Isabelle Casademont, Fanny Koeth, Marina Penova, Kanchana Tangnararatchakit, Chiea Chuen Khor, Richard Paul, Prida Malasit, Fumihiko Matsuda, Etienne Simon-Lorière, Prapat Suriyaphol, Luisa Pereira, Anavaj Sakuntabhai
Ethnic diversity has been long considered as one of the factors explaining why the severe forms of dengue are more prevalent in Southeast Asia than anywhere else. Here we take advantage of the admixed profile of Southeast Asians to perform coupled association-admixture analyses in Thai cohorts. For dengue shock syndrome (DSS), the significant haplotypes are located in genes coding for phospholipase C members (PLCB4 added to previously reported PLCE1), related to inflammation of blood vessels. For dengue fever (DF), we found evidence of significant association with CHST10, AHRR, PPP2R5E and GRIP1 genes, which participate in the xenobiotic metabolism signaling pathway...
February 2018: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/29446025/healing-potential-of-adiantum-capillus-veneris-l-plant-extract-on-bisphenol-a-induced-hepatic-toxicity-in-male-albino-rats
#7
Qudsia Kanwal, Abdul Qadir, Amina, Asmatullah, Hafiza Hira Iqbal, Bushra Munir
Bisphenol A (BPA) is a widely used environmental pollutant in the production of plastics but causes hepatotoxicity in mammals. In the present study, we studied the BPA-induced oxidative stress in rats and ameliorative potential of Adiantum capillus-veneris L. plant. It was concluded that the BPA can reduce the body and liver weight, increase in biochemical levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), total bilirubin, and disturb the normal hepatic physiology, histology, and metabolism...
February 14, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29445375/the-role-of-cytochromes-p450-in-infection
#8
REVIEW
Elisavet Stavropoulou, Gratiela G Pircalabioru, Eugenia Bezirtzoglou
Cytochromes are expressed in many different tissues of the human body. They are found mostly in intestinal and hepatic tissues. Cytochromes P450 (CYPs) are enzymes that oxidize substances using iron and are able to metabolize a large variety of xenobiotic substances. CYP enzymes are linked to a wide array of reactions including and O-dealkylation, S-oxidation, epoxidation, and hydroxylation. The activity of the typical P450 cytochrome is influenced by a variety of factors, such as genus, environment, disease state, herbicide, alcohol, and herbal medications...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29443110/imaging-approaches-to-assessments-of-toxicological-oxidative-stress-using-genetically-encoded-fluorogenic-sensors
#9
Elizabeth M Corteselli, James M Samet, Eugene A Gibbs-Flournoy
While oxidative stress is a commonly cited toxicological mechanism, conventional methods to study it suffer from a number of shortcomings, including destruction of the sample, introduction of potential artifacts, and a lack of specificity for the reactive species involved. Thus, there is a current need in the field of toxicology for non-destructive, sensitive, and specific methods that can be used to observe and quantify intracellular redox perturbations, more commonly referred to as oxidative stress. Here, we present a method for the use of two genetically-encoded fluorogenic sensors, roGFP2 and HyPer, to be used in live-cell imaging studies to observe xenobiotic-induced oxidative responses...
February 7, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29441869/monosodium-glutamate-induced-obesity-changed-the-expression-and-activity-of-glutathione-s-transferases-in-mouse-heart-and-kidney
#10
I Boušová, Š Košťáková, P Matoušková, H Bártíková, B Szotáková, L Skálová
Obesity may affect activity and/or expression of enzymes participating in xenobiotics' detoxification and antioxidant defense. This study sought to investigate the activities and expression of cardiac and renal glutathione S-transferase (GST) isoforms in order to reveal possible differences between obese and control mice. For this purpose, mice with monosodium glutamate (MSG)-induced obesity were used as an experimental model. Obesity was induced in newborn male mice by repeated s.c. administration of MSG. At 8 months of age, mice were sacrificed and specific activity, protein and mRNA expressions levels of GSTs were analyzed in their heart and kidney...
May 1, 2017: Die Pharmazie
https://www.readbyqxmd.com/read/29440179/role-of-c-jun-n-terminal-kinase-in-pregnane-x-receptor-mediated-induction-of-human-cytochrome-p4503a4-in-vitro
#11
Guncha Taneja, Chun Chu, Paramahamsa Maturu, Bhagavatula Moorthy, Romi Ghose
Cytochrome P450 (CYP) 3A4 is the most abundant drug metabolizing enzyme and is responsible for the metabolism of ~50% of clinically available drugs. Induction of CYP3A4 impacts the disposition of its substrates and leads to harmful clinical consequences such as failure of therapy. In order to prevent such undesirable consequences, molecular mechanisms of regulation of CYP3A4 need to be fully understood. CYP3A4 induction is primarily regulated by the xenobiotic nuclear receptor, pregnane-X-receptor (PXR). After ligand binding, PXR is transported to the nucleus, where it binds to the CYP3A4 promoter and induces its gene expression...
February 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29440178/evaluation-of-alteration-in-hepatic-and-intestinal-bcrp-function-in-vivo-due-to-abcg2-c-421c-a-polymorphism-based-on-pbpk-analysis-of-rosuvastatin
#12
Azusa Futatsugi, Kota Toshimoto, Takashi Yoshikado, Yuichi Sugiyama, Yukio Kato
Polymorphism c.421C>A in ABCG2 gene is thought to reduce the activity of breast cancer resistance protein (BCRP), a xenobiotic transporter, although it is not clear which organ(s) contributes to the polymorphism-associated pharmacokinetic change. The aim of the present study was to quantitatively estimate the influence of c.421C>A on intestinal and hepatic BCRP activity, using a physiologically based pharmacokinetic (PBPK) model of rosuvastatin developed from clinical data and several in vitro studies...
February 12, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29439084/evaluating-the-impact-of-type-2-diabetes-mellitus-on-cyp450-metabolic-activities-protocol-for-a-case-control-pharmacokinetic-study
#13
Sophie Gravel, Jean-Louis Chiasson, Suzanne Dallaire, Jacques Turgeon, Veronique Michaud
INTRODUCTION: Diabetes affects more than 9% of the adult population worldwide. Patients with type 2 diabetes mellitus (T2DM) show variable responses to some drugs which may be due, in part, to variability in the functional activity of drug-metabolising enzymes including cytochromes P450 (CYP450s). CYP450 is a superfamily of enzymes responsible for xenobiotic metabolism. Knowledge must be gained on the impact of T2DM and related inflammatory processes on drug metabolism and its consequences on drug response...
February 8, 2018: BMJ Open
https://www.readbyqxmd.com/read/29438977/posttranscriptional-regulation-of-ugt2b10-hepatic-expression-and-activity-by-alternative-splicing
#14
Adrien Labriet, Eric P Allain, Michele Rouleau, Yannick Audet-Delage, Lyne Villeneuve, Chantal Guillemette
The detoxification enzyme UDP-glucuronosyltransferase UGT2B10 is specialized in the N-linked glucuronidation of many drugs and xenobiotics. Preferred substrates possess tertiary aliphatic amines and heterocyclic amines such as tobacco carcinogens and several anti-depressants and anti-psychotics. We hypothesized that alternative splicing (AS) constitutes a mean to regulate steady state levels of UGT2B10 and enzyme activity. We established the transcriptome of UGT2B10 in normal and tumoral tissues of multiple individuals...
February 9, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29438444/systems-genomics-study-reveals-expression-quantitative-trait-loci-regulator-genes-and-pathways-associated-with-boar-taint-in-pigs
#15
Markus Drag, Mathias B Hansen, Haja N Kadarmideen
Boar taint is an offensive odour and/or taste from a proportion of non-castrated male pigs caused by skatole and androstenone accumulation during sexual maturity. Castration is widely used to avoid boar taint but is currently under debate because of animal welfare concerns. This study aimed to identify expression quantitative trait loci (eQTLs) with potential effects on boar taint compounds to improve breeding possibilities for reduced boar taint. Danish Landrace male boars with low, medium and high genetic merit for skatole and human nose score (HNS) were slaughtered at ~100 kg...
2018: PloS One
https://www.readbyqxmd.com/read/29435799/influence-of-land-use-on-the-health-of-a-detritivorous-fish-ancistrus-mullerae-endemic-to-the-iguassu-ecoregion-relationship-between-agricultural-land-use-and-severe-histopathological-alterations
#16
Mayara Pereira Neves, João Paulo de Arruda Amorim, Rosilene Luciana Delariva
This study aimed to evaluate the histopathological biomarkers of the gills and liver of endemic catfish to test the hypothesis that, in environments under intense land use by agricultural activities, histopathological alterations occur more severely. Samples were collected by electrofishing in seven streams in the Lower Iguaçu basin quarterly from August 2015 to February 2016. The gills and livers were processed according to routine histological methods and examined by light microscopy. The histopathological alterations observed in fish from the streams with a higher percentage of natural vegetation cover were considered modest and indicated normal functioning of the organ (such as edema, hyperplasia, and leukocyte infiltration)...
February 12, 2018: Environmental Science and Pollution Research International
https://www.readbyqxmd.com/read/29434939/identification-of-metabolism-associated-genes-and-pathways-involved-in-different-stages-of-clear-cell-renal-cell-carcinoma
#17
Hui-Juan Li, Wen-Xing Li, Shao-Xing Dai, Yi-Cheng Guo, Jun-Juan Zheng, Jia-Qian Liu, Qian Wang, Bi-Wen Chen, Gong-Hua Li, Jing-Fei Huang
The lack of early diagnostic markers and novel therapeutic targets for clear cell renal cell carcinoma (ccRCC) negatively affects patient prognosis. Cancer metabolism is an attractive area for the understanding of the molecular mechanism of carcinogenesis. The present study attempted to identify metabolic changes from the view of the expression of metabolism-associated genes between control samples and those of ccRCC at different disease stages. Data concerning ccRCC gene expression obtained by RNA-sequencing was obtained from The Cancer Genome Atlas and data on metabolism-associated genes were extracted using the Recon2 model...
February 2018: Oncology Letters
https://www.readbyqxmd.com/read/29434350/the-factors-driving-evolved-herbicide-resistance-at-a-national-scale
#18
Helen L Hicks, David Comont, Shaun R Coutts, Laura Crook, Richard Hull, Ken Norris, Paul Neve, Dylan Z Childs, Robert P Freckleton
Repeated use of xenobiotic chemicals has selected for the rapid evolution of resistance, threatening health and food security at a global scale. Strategies for preventing the evolution of resistance include cycling and mixtures of chemicals and diversification of management. We currently lack large-scale studies that evaluate the efficacy of these different strategies for minimizing the evolution of resistance. Here we use a national-scale data set of occurrence of the weed Alopecurus myosuroides (black-grass) in the United Kingdom to address this...
February 12, 2018: Nature Ecology & Evolution
https://www.readbyqxmd.com/read/29432141/structure-and-function-of-the-cytochrome-p450-peroxygenase-enzymes
#19
REVIEW
Andrew W Munro, Kirsty J McLean, Job L Grant, Thomas M Makris
The cytochromes P450 (P450s or CYPs) constitute a large heme enzyme superfamily, members of which catalyze the oxidative transformation of a wide range of organic substrates, and whose functions are crucial to xenobiotic metabolism and steroid transformation in humans and other organisms. The P450 peroxygenases are a subgroup of the P450s that have evolved in microbes to catalyze the oxidative metabolism of fatty acids, using hydrogen peroxide as an oxidant rather than NAD(P)H-driven redox partner systems typical of the vast majority of other characterized P450 enzymes...
February 6, 2018: Biochemical Society Transactions
https://www.readbyqxmd.com/read/29431616/role-of-the-pregnane-x-receptor-in-binge-ethanol-induced-steatosis-and-hepatotoxicity
#20
Sora Choi, Afua A Gyamfi, Prince Neequaye, Samuel Addo, Frank J Gonzalez, Maxwell A Gyamfi
The pregnane X receptor (PXR, NR1I2) is a xenobiotic-sensing nuclear receptor that defends against toxic agents. We have shown that PXR promotes chronic ethanol (EtOH)-induced steatosis. Therefore, we examined the role of PXR in binge EtOH-induced hepatotoxicity. Male wild type (WT) and Pxr-null mice were orally administered three binge doses of EtOH (4.5 g/kg, every 12 hours) and euthanized four hours after the final dose. Pxr-null mice displayed higher basal mRNA levels of hepatic lipogenic transcription factor sterol regulatory element binding protein 1c (Srebp-1c) and its target stearoyl-CoA desaturase 1 (Scd1) and the lipid peroxide detoxifying aldo-keto reductase 1b7 (Akr1b7) and higher protein levels of EtOH-metabolizing alcohol dehydrogenase 1 (ADH1)...
February 5, 2018: Journal of Pharmacology and Experimental Therapeutics
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