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Cytochrome P450

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https://www.readbyqxmd.com/read/27920888/development-of-a-high-resolution-melting-analysis-method-for-cyp2c19-17-genotyping-in-healthy-volunteers
#1
Zahra Ghasemi, Mehrdad Hashemi, Mahsa Ejabati, Seyyed Meisam Ebrahimi, Hamidreza Kheiri Manjili, Ali Sharafi, Ali Ramazani
BACKGROUND: Genetic polymorphisms of drug metabolisms by cytochrome P450 (P450s) could affect drug response, attracting particular interest in the pharmacogenetics. Due to the importance of CYP2C19* 17 allele and its capability of super- fast metabolism and also lack of information about distribution of the alleles in Iranian population, this research aimed to use High Resolution Melting (HRM) method compared to PCR-RFLP for genotyping healthy Iranian population. METHODS: Blood samples were collected from 100 healthy Iranian volunteers...
October 2016: Avicenna Journal of Medical Biotechnology
https://www.readbyqxmd.com/read/27920817/pharmacological-characterization-of-liquiritigenin-a-chiral-flavonoid-in-licorice
#2
Samaa Alrushaid, Neal M Davies, Stephanie E Martinez, Casey L Sayre
Liquiritigenin is a chiral flavonoid present in plant based food, nutraceuticals, and traditional medicines. It is also an important ingredient present in licorice. The purpose of this study is to explore the pharmacological activity of racemic liquiritigenin utilizing several in vitro assays with relevant roles in colon cancer and diabetes. Where possible, the pure enantiomers were tested to identify the stereospecific contribution to the activity. In vitro antioxidant, anticancer, anti-inflammatory activities (cyclooxygenase inhibition), antidiabetic activities (alpha-amylase and alpha-glucosidase inhibition) as well as cytochrome P450 (CYP450) inhibitory activities were assessed...
October 2016: Research in Pharmaceutical Sciences
https://www.readbyqxmd.com/read/27919191/phytotherapeutic-approach-a-new-hope-for-polycyclic-aromatic-hydrocarbons-induced-cellular-disorders-autophagic-and-apoptotic-cell-death
#3
Durgesh Nandini Das, Prashanta Kumar Panda, Prajna Paramita Naik, Subhadip Mukhopadhyay, Niharika Sinha, Sujit K Bhutia
Polycyclic aromatic hydrocarbons (PAHs) comprise the major class of cancer-causing chemicals and are ranked ninth among the chemical compounds threatening to humans. Moreover, interest in PAHs has been mainly due to their carcinogenic property, these compounds are genotoxic, teratogenic, mutagenic, and carcinogenic. Polymorphism in cytochrome P450 (CYP450) and aryl hydrocarbon receptor (AhR) have the capacity to convert procarcinogens into carcinogens, which is an imperative factor contributing to individual susceptibility to cancer development...
December 5, 2016: Toxicology Mechanisms and Methods
https://www.readbyqxmd.com/read/27919007/challenges-in-assignment-of-allosteric-effects-in-cytochrome-p450-catalyzed-substrate-oxidations-to-structural-dynamics-in-the-hemoprotein-architecture
#4
Peter Hlavica
Cytochrome P450s (CYP) represent a superfamily of b-type hemoproteins catalyzing NAD(P)H-dependent oxidative biotransformation of a vast array of natural and xenobiotic compounds. Many eu- and prokaryotic members of this class of monooxygenases display complex non-Michaelis-Menten saturation kinetics, suggestive of homo-/heterotropic cooperativity arising from substrate-/effector-induced allosteric interactions. Here, the paradigm of multiple-ligand occupancy of the catalytic pocket in combination with enzyme oligomerization provides the most favored explanations for the atypical kinetic patterns...
November 25, 2016: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/27918912/predicting-cyp2d6-phenotype-from-resting-brain-perfusion-images-by-gradient-boosting
#5
Giulio Napolitano, Julia C Stingl, Matthias Schmid, Roberto Viviani
The cytochrome P450 enzyme 2D6 is involved in the metabolism of 20% of all commonly used drugs, including many psychotropic drugs and CNS-active substances. CYP2D6 is among the CYP enzymes with the highest expression levels in the brain, suggesting a role in the local brain metabolism of psychotropic drugs and the existence of endogenous substrates. The genetic polymorphism of CYP2D6, which causes individual differences in activity levels of the enzyme, has also been characterized functionally in human brain imaging studies...
November 22, 2016: Psychiatry Research
https://www.readbyqxmd.com/read/27918126/versatile-trityl-spin-labels-for-nanometer-distance-measurements-on-biomolecules-in%C3%A2-vitro-and-within-cells
#6
J Jacques Jassoy, Andreas Berndhäuser, Fraser Duthie, Sebastian P Kühn, Gregor Hagelueken, Olav Schiemann
Structure determination of biomacromolecules under in-cell conditions is a relevant yet challenging task. Electron paramagnetic resonance (EPR) distance measurements in combination with site-directed spin labeling (SDSL) are a valuable tool in this endeavor but the usually used nitroxide spin labels are not well-suited for in-cell measurements. In contrast, triarylmethyl (trityl) radicals are highly persistent, exhibit a long relaxation time and a narrow spectral width. Here, the synthesis of a versatile collection of trityl spin labels and their application in in vitro and in-cell trityl-iron distance measurements on a cytochrome P450 protein are described...
December 5, 2016: Angewandte Chemie
https://www.readbyqxmd.com/read/27918111/imatinib-accelerates-progenitor-cell-mediated-liver-regeneration-in-choline-deficient-ethionine-supplemented-diet-fed-mice
#7
András Rókusz, Edina Bugyik, Vanessza Szabó, Armanda Szücs, Sándor Paku, Péter Nagy, Katalin Dezső
Severe chronic hepatic injury can induce complex reparative processes. Ductular reaction and the appearance of small hepatocytes are standard components of this response, which is thought to have both adverse (e.g. fibrosis, carcinogenesis) and beneficial (regeneration) consequences. This complex tissue reaction is regulated by orchestrated cytokine action. We have investigated the influence of the tyrosine kinase inhibitor imatinib on a regenerative process. Ductular reaction was induced in mice by the widely used choline-deficient ethionine-supplemented diet (CDE)...
December 5, 2016: International Journal of Experimental Pathology
https://www.readbyqxmd.com/read/27916218/fenofibrate-attenuates-malignant-hypertension-by-suppression-of-the-renin-angiotensin-system-a-study-in-cyp1a1-ren-2-transgenic-rats
#8
Šárka Jíchová, Šárka Doleželová, Libor Kopkan, Elzbieta Kompanowska-Jezierska, Janusz Sadowski, Luděk Červenka
BACKGROUND: Malignant hypertension is a life-threatening condition, and its pathophysiology is still poorly understood. The present study was designed to evaluate the role of interaction of the renin-angiotensin system with 20-hydroxyeicosatetraenoic acid (20-HETE), a product of cytochrome P450 (CYP)-dependent ω-hydroxylase pathway, in the pathophysiology of angiotensin II (ANG II)-dependent malignant hypertension in Cyp1a1-Ren-2 transgenic rats. METHODS: Malignant hypertension was induced by 12 days׳ dietary administration of 0...
December 2016: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/27915193/metabolic-fate-and-detectability-of-the-new-psychoactive-substances-2-4-bromo-2-5-dimethoxyphenyl-n-2-methoxyphenyl-methyl-ethanamine-25b-nbome-and-2-4-chloro-2-5-dimethoxyphenyl-n-2-methoxyphenyl-methyl-ethanamine-25c-nbome-in-human-and-rat-urine-by-gc-ms
#9
Achim T Caspar, Simon D Brandt, Andreas E Stoever, Markus R Meyer, Hans H Maurer
25B-NBOMe and 25C-NBOMe are potent 5-HT2A receptor agonists that have been associated with inducing hallucinogenic effects in drug users and severe intoxications. This paper describes the identification of their metabolites in rat and human urine by liquid chromatography (LC)-high resolution (HR)-MS/MS, the comparison of metabolite formation in vitro and in vivo and in different species, the general involvement of human cytochrome-P450 (CYP) isoenzymes on their metabolism steps, and their detectability by standard urine screening approaches (SUSAs) using GC-MS, LC-MS(n), or LC-HR-MS/MS...
November 27, 2016: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/27914545/potential-mode-of-action-of-a-novel-plumbagin-as-a-mosquito-repellent-against-the-malarial-vector-anopheles-stephensi-culicidae-diptera
#10
Venkatraman Pradeepa, Sengottayan Senthil-Nathan, Subbiah Sathish-Narayanan, Selvaraj Selin-Rani, Prabhakaran Vasantha-Srinivasan, Annamalai Thanigaivel, Athirstam Ponsankar, Edward-Sam Edwin, Muthiah Sakthi-Bagavathy, Kandaswamy Kalaivani, Kadarkarai Murugan, Veeramuthu Duraipandiyan, Naif Abdullah Al-Dhabi
Plumbagin was isolated and characterized from the roots of Plumbago zeylanica using chromatography: TLC, Column chromatogram, HPLC, FTIR and (1)H NMR. The isolated pure compounds were assayed for potency as inhibitors of: acetylcholine esterase (AchE), glutathione S-transferases (GST), superoxide dismutase (SOD), cytochrome P450 and α, β-esterase, and for repellency with Anopheles stephensi at four different concentrations (25, 50, 75 and 100ppm). The enzyme assay against the pure compound reveals that the level of esterase and SOD was decreased significantly in contrast the level of GST and cytochrome P450 was increased significantly...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27914535/indoxacarb-biotransformation-in-the-german-cockroach
#11
Ameya D Gondhalekar, Ernesto S Nakayasu, Isabel Silva, Bruce Cooper, Michael E Scharf
Insecticides that are used for pest control undergo physical and biological (enzymatic) degradation. Indoxacarb is an oxadiazine class sodium channel blocker insecticide used for German cockroach (Blattella germanica L.) control. At present, no information is available on enzymatic biotransformation or metabolism of indoxacarb in this important urban pest. We studied the biotransformation pathways of indoxacarb in one susceptible and three field strains with varying susceptibility levels using liquid chromatography and high-resolution mass spectrometry...
November 2016: Pesticide Biochemistry and Physiology
https://www.readbyqxmd.com/read/27913826/partial-gene-sequencing-of-cyp1a-vitellogenin-and-metallothionein-in-mosquitofish-gambusia-yucatana-and-gambusia-sexradiata
#12
Roberto Vázquez-Euán, Karla S Escalante-Herrera, Gabriela Rodríguez-Fuentes
Ground characteristics in the Yucatan Peninsula make recovery and treatment of wastewater very expensive. This situation has contributed to an increase of pollutants in the aquifer. Unfortunately, studies related to the effects of those pollutants in native organisms are scarce. The aim of this work was to obtain partial sequences of widely known genes used as biomarkers of pollutant effect in Gambusia yucatana and Gambusia sexradiata. The studied genes were: cytochrome P450 1A (CYP1A); vitellogenin (VTG); metallothionein (MT), and two housekeeping genes, 18S and β-actin...
December 2, 2016: Bulletin of Environmental Contamination and Toxicology
https://www.readbyqxmd.com/read/27913210/trpv4-activation-of-endothelial-nitric-oxide-synthase-resists-nonalcoholic-fatty-liver-disease-by-blocking-cyp2e1-mediated-redox-toxicity
#13
Ratanesh K Seth, Suvarthi Das, Diptadip Dattaroy, Varun Chandrashekaran, Firas Alhasson, Gregory Michelotti, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Darwin P Bell, Wolfgang Liedtke, Saurabh Chatterjee
NAFLD is a clinically progressive disease with steatosis, inflammation, endothelial dysfunction and fibrosis being the stages where clinical intervention becomes necessary. Lack of early biomarkers and absence of a FDA approved drug obstructs efforts for effective treatment. NAFLD progression is strongly linked to a balance between liver injury, tissue regeneration and the functioning of endogenous defense mechanisms. The failure of the defense pathways to resist the tissue damage arising from redox stress, one of the "multiple hits" in disease progression, give rise to heightened inflammation and occasional fibrosis...
November 29, 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27913146/effects-of-high-fat-diet-on-plasma-profiles-of-eicosanoid-metabolites-in-mice
#14
Weicang Wang, Jun Yang, Haixia Yang, Katherine Z Sanidad, Bruce D Hammock, Daeyoung Kim, Guodong Zhang
Obesity is a serious health problem in the US and is associated with increased risks of various human diseases. To date, the mechanisms by which obesity increases the risks of a wide range of human diseases are not well understood. Here we used a LC-MS/MS-based lipidomics, which can analyze >100 bioactive lipid mediators produced by cyclooxygenase, lipoxygenase, and cytochrome P450 enzymes, to analyze plasma profiles of lipid mediators in high-fat diet induced obesity in C57BL/6 mice. Our results show that the plasma concentrations of epoxyoctadecenoic acids (EpOMEs, also termed as leukotoxins) are significantly increased in plasma of high-fat diet-fed mice, in addition, EpOMEs are among the most abundant lipid mediators detected in mouse plasma...
November 30, 2016: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/27910907/micrornas-modulate-adaption-to-multiple-abiotic-stresses-in-chlamydomonas-reinhardtii
#15
Xiang Gao, Fengge Zhang, Jinlu Hu, Wenkai Cai, Ge Shan, Dongsheng Dai, Kaiyao Huang, Gaohong Wang
MicroRNAs play an important role in abiotic stress responses in higher plants and animals, but their role in stress adaptation in algae remains unknown. In this study, the expression of identified and putative miRNAs in Chlamydomonas reinhardtii was assessed using quantitative polymerase chain reaction; some of the miRNAs (Cre-miR906-3p) were up-regulated, whereas others (Cre-miR910) were down-regulated when the species was subjected to multiple abiotic stresses. With degradome sequencing data, we also identified ATP4 (the d-subunit of ATP synthase) and NCR2 (NADPH: cytochrome P450 reductase) as one of the several targets of Cre-miR906-3p and Cre-miR910, respectively...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27910036/evaluation-of-the-pharmacokinetic-interaction-between-venetoclax-a-selective-bcl-2-inhibitor-and-warfarin-in-healthy-volunteers
#16
Ahmed Hamed Salem, Beibei Hu, Kevin J Freise, Suresh K Agarwal, Dilraj S Sidhu, Shekman L Wong
BACKGROUND AND OBJECTIVE: Venetoclax is a selective, B-cell lymphoma-2 inhibitor that has demonstrated clinical efficacy in a variety of hematological malignancies. In vitro data indicated weak cytochrome P450 (CYP) 2C9 inhibition by venetoclax; however, it is not predicted to cause clinically relevant inhibition due to high plasma protein binding. A Phase 1 study was conducted in healthy volunteers to evaluate the effect of venetoclax on warfarin pharmacokinetics. METHODS: Subjects received a single oral dose of 5 mg warfarin on day 1 of both periods 1 and 2, separated by a 14 days washout...
December 2, 2016: Clinical Drug Investigation
https://www.readbyqxmd.com/read/27909995/solithromycin-a-novel-fluoroketolide-for-the-treatment-of-community-acquired-bacterial-pneumonia
#17
REVIEW
George G Zhanel, Erika Hartel, Heather Adam, Sheryl Zelenitsky, Michael A Zhanel, Alyssa Golden, Frank Schweizer, Bala Gorityala, Philippe R S Lagacé-Wiens, Andrew J Walkty, Alfred S Gin, Daryl J Hoban, Joseph P Lynch, James A Karlowsky
Solithromycin is a novel fluoroketolide developed in both oral and intravenous formulations to address increasing macrolide resistance in pathogens causing community-acquired bacterial pneumonia (CABP). When compared with its macrolide and ketolide predecessors, solithromycin has several structural modifications which increase its ribosomal binding and reduce its propensity to known macrolide resistance mechanisms. Solithromycin, like telithromycin, affects 50S ribosomal subunit formation and function, as well as causing frame-shift errors during translation...
December 1, 2016: Drugs
https://www.readbyqxmd.com/read/27907843/triphenyltin-degradation-and-proteomic-response-by-an-engineered-escherichia-coli-expressing-cytochrome-p450-enzyme
#18
Wenying Yi, Kunliang Yang, Jinshao Ye, Yan Long, Jing Ke, Huase Ou
Although triphenyltin (TPT) degradation pathway has been determined, information about the enzyme and protein networks involved was severely limited. To this end, a cytochrome P450 hydroxylase (CYP450) gene from Bacillus thuringiensis was cloned and expressed in Escherichia coli BL21 (DE3), namely E. coli pET32a-CYP450, whose dosage at 1gL(-1) could degrade 54.6% TPT at 1mgL(-1) within 6 d through attacking the carbon-tin bonds of TPT by CYP450. Sequence analysis verified that the CYP450 gene had a 1214bp open reading frame, encoding a protein with 404 amino acids...
November 28, 2016: Ecotoxicology and Environmental Safety
https://www.readbyqxmd.com/read/27907195/novel-aryl-hydrocarbon-receptor-agonist-suppresses-migration-and-invasion-of-breast-cancer-cells
#19
Hamza Hanieh, Omar Mohafez, Villianur Ibrahim Hairul-Islam, Abdullah Alzahrani, Mohammad Bani Ismail, Krishnaraj Thirugnanasambantham
BACKGROUND: Despite the remarkable progress to fight against breast cancer, metastasis remains the dominant cause of treatment failure and recurrence. Therefore, control of invasiveness potential of breast cancer cells is crucial. Accumulating evidences suggest Aryl hydrocarbon receptor (Ahr), a helix-loop-helix transcription factor, as a promising target to control migration and invasion in breast cancer cells. Thus, an Ahr-based exploration was performed to identify a new Ahr agonist with inhibitory potentials on cancer cell motility...
2016: PloS One
https://www.readbyqxmd.com/read/27904981/candida-guilliermondii-as-a-potential-biocatalyst-for-the-production-of-long-chain-%C3%AE-%C3%AF-dicarboxylic-acids
#20
Nicole Werner, Miriam Dreyer, Wenke Wagner, Nicolas Papon, Steffen Rupp, Susanne Zibek
OBJECTIVES: To explore Candida guilliermondii for the production of long-chain dicarboxylic acids (DCA), we performed metabolic pathway engineering aiming to prevent DCA consumption during β-oxidation, but also to increase its production via the ω-oxidation pathway. RESULTS: We identified the major β- and ω-oxidation pathway genes in C. guilliermondii and performed first steps in the strain improvement. A double pox disruption mutant was created that slowed growth with oleic acid but showed accelerated DCA degradation...
November 30, 2016: Biotechnology Letters
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