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CYP450 enzymes

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https://www.readbyqxmd.com/read/30551694/cytochrome-p450-cyp450-2d6-a-n-acetyltransferase-2-nat2-7-a-and-multidrug-resistance-1-mdr1-3435-t-alleles-collectively-increase-risk-of-ulcerative-colitis
#1
Farzaneh Lotfi, Fariborz Bahrehmand, Asad Vaisi-Raygani, Reza Khodarahmi, Maryam Tanhapour, Amir Kiani, Zohreh Rahimi, Tayebeh Pourmotabbed
BACKGROUND: Discovering the association between genetic variations of metabolizing enzymes with idiopathic diseases such as ulcerative colitis (UC) may not only be an auxiliary agent in diagnosis but also could be an effective pharmacotherapy for inflammatory bowel disease (IBD). The aim of the present case-control study was to determine the association of cytochrome P450 2D6 (CYP2D6 *4), N-acteyltransferase-2 (NAT2*7) and multidrug resistance 1 (MDR1) 3435 C/T genotypes with UC susceptibility and thiopurine methyltransferase (TPMT) enzyme activity...
November 1, 2018: Archives of Iranian Medicine
https://www.readbyqxmd.com/read/30532780/differential-expression-of-prostaglandin-i2-synthase-associated-with-arachidonic-acid-pathway-in-the-oral-squamous-cell-carcinoma
#2
Anelise Russo, Patrícia M Biselli-Chicote, Rosa S Kawasaki-Oyama, Márcia M U Castanhole-Nunes, José V Maniglia, Dalísio de Santi Neto, Érika C Pavarino, Eny M Goloni-Bertollo
Introduction: Differential expression of genes encoding cytochrome P450 (CYP) and other oxygenases enzymes involved in biotransformation mechanisms of endogenous and exogenous compounds can lead to oral tumor development. Objective: We aimed to identify the expression profile of these genes, searching for susceptibility biomarkers in oral squamous cell carcinoma. Patients and Methods: Sixteen oral squamous cell carcinoma samples were included in this study (eight tumor and eight adjacent non-tumor tissues)...
2018: Journal of Oncology
https://www.readbyqxmd.com/read/30532626/novel-plant-inducers-of-pxr-dependent-cytochrome-p450-3a4-expression-in-hepg2-cells
#3
Mohammed S Al-Dosari, Mohammad K Parvez
The cytochrome P450 3A4 (CYP3A4) is the most abundant CYP450 enzyme involved in the metabolism of endogenous products and xenobiotics, including prescription drugs and herbals. Modulation of hepatic CYP3A4 gene expression via nuclear receptors, like pregnane X receptor (PXR), is a major cause of adverse effects like drug-unresponsiveness and toxicity. In the present study, ethanol extracts of 58 medicinal plants, belonging to 27 families, were evaluated for potential activities in CYP3A4 induction in HepG2 cells by reporter gene assay...
December 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
https://www.readbyqxmd.com/read/30526461/computer-aided-drug-designing-for-the-identification-of-high-affinity-small-molecule-targeting-cd20-for-the-clinical-treatment-of-chronic-lymphocytic-leukemia-cll
#4
Kritika Sinha, Manisha Majhi, Garima Thakur, Khushboo Patidar, Jajoriya Sweta, Anuraj Nayarisseri, Sanjeev Kumar Singh
BACKGROUND: Chronic lymphocytic leukemia (CLL) is a B-lineage lymphoid malignancy of self-reactive cells that are focused to produce polyreactive natural auto antibodies. Its surface protein marker CD20 plays an important role in the humoral immune response, targeting which have emerged as an attractive therapeutic option for the treatment of CLL. The present study explains the interaction of the CD20 with its established inhibitors and to discover the compound having high binding affinity against the target protein receptor...
December 10, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30524481/chemical-composition-and-antifungal-in-vitro-and-in-silico-antioxidant-and-anticholinesterase-activities-of-extracts-and-constituents-of-ouratea-fieldingiana-dc-baill
#5
José Eranildo Teles do Nascimento, Ana Livya Moreira Rodrigues, Daniele Silva de Lisboa, Hortência Ribeiro Liberato, Maria José Cajazeiras Falcão, Cecília Rocha da Silva, Hélio Vitoriano Nobre Júnior, Raimundo Braz Filho, Valdir Ferreira de Paula Junior, Daniela Ribeiro Alves, Selene Maia de Morais
Ouratea fieldingiana (Gardner) Engl is popularly used for wound healing. This study describes the main chemical compounds present in extracts of O. fieldingiana and evaluates their biological potential by investigating antifungal, antioxidant, and anticholinesterase activities. The action mechanism of main antifungal compound was investigated by molecular docking using the enzyme sterol 14- α demethylase, CYP51, required for ergosterol biosynthesis. The seeds and leaves were extracted with ethanol in a Soxhlet apparatus and by maceration, respectively...
2018: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/30521883/cytochrome-p450-epoxygenases-and-cancer-a-genetic-and-a-molecular-perspective
#6
REVIEW
Lindsay N Sausville, Scott M Williams, Ambra Pozzi
Cytochrome CYP450 epoxygenases catalyze the epoxidation of polyunsaturated fatty acids including arachidonic acid, eicosapentaenoic acid, and docosahexaenoic acid. The arachidonic acid-derived products are potent pro-angiogenic lipids and promote tumor development and growth. On the other hand, eicosapentaenoic acid- and docosahexaenoic acid-derived products inhibit angiogenesis and play a protective role in certain pathological conditions including cancer. Increased expression of CYP2C epoxygenases, together with increased levels of their arachidonic acid-derived products, is often observed in tumors and tumor-associated vasculature, making these enzymes an ideal target for anti-cancer therapies...
December 3, 2018: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/30513965/de-novo-biosynthesis-of-p-coumaric-acid-in-e-coli-with-a-trans-cinnamic-acid-4-hydroxylase-from-the-amaryllidaceae-plant-lycoris-aurea
#7
Yikui Li, Jie Li, Binbin Qian, Li Cheng, Sheng Xu, Ren Wang
p -Coumaric acid is a commercially available phenolcarboxylic acid with a great number of important applications in the nutraceutical, pharmaceutical, material and chemical industries. p -Coumaric acid has been biosynthesized in some engineered microbes, but the potential of the plant CYP450-involved biosynthetic route has not investigated in Escherichia coli . In the present study, a novel trans -cinnamic acid 4-hydroxylase (C4H) encoding the Lau C4H gene was isolated from Lycoris aurea (L' Hér.) Herb via rapid amplification of cDNA ends...
December 3, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/30511429/an-overexpressed-cytochrome-p450-cyp439a1v3-confers-deltamethrin-resistance-in-laodelphax-striatellus-fall%C3%A3-n-hemiptera-delphacidae
#8
Mohammad Asaduzzaman Miah, Mohammed Esmail Abdalla Elzaki, Asmaul Husna, Zhaojun Han
Deltamethrin resistance in Laodelphax striatellus had been associated with its oxidative detoxification by overexpression of four cytochrome P450 monooxygenases like CYP353D1v2, CYP6FU1, CYP6AY3v2, and CYP439A1v3. The first three P450s have been validated for insecticide-metabolizing capability and only CYP6FU1 was found to degrade deltamethrin. In this study, an investigation was conducted to confirm the capability of CYP439A1v3 to degrade deltamethrin. The CYP439A1v3 was first expressed in Sf9 cell line and its recombinant enzyme was tested for metabolic activity against different insecticides using substrate depletion assay combined with metabolite identification...
December 4, 2018: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/30499388/biology-of-heme-drug-interactions-and-adverse-drug-reactions-with-cyp450
#9
Neeraj Kumar, Heerak Chugh, Damini Sood, Aarushi Singh, Ravi Tomar, Vartika Tomar, Ramesh Chandra
Heme is central to functions of many biologically important enzymes (hemoproteins). It is an assembly of four porphyrin rings joined through methylene bridges with a central Fe (II). Heme is present in all cells, and its synthesis and degradation balance its amount in the cell. The deregulations of heme networks and incorporation in hemoproteins lead to pathogenic state. This article addresses the detailed structure, biosynthesis, degradation, and transportation associated afflictions to heme. The article is followed by its roles in various diseased conditions where it is produced mainly as the cause of increased hemolysis...
November 29, 2018: Current Topics in Medicinal Chemistry
https://www.readbyqxmd.com/read/30479202/clinical-utility-of-pharmacogenetic-testing-and-a-clinical-decision-support-tool-to-enhance-the-identification-of-drug-therapy-problems-through-medication-therapy-management-in-polypharmacy-patients
#10
Kibum Kim, Jonathan W Magness, Ryan Nelson, Valerie Baron, Diana I Brixner
BACKGROUND: In polypharmacy patients, medication therapy management (MTM) services provide a comprehensive review of current medications and future treatment goals. Pharmacogenetics (PGx) may further optimize the identification of potential drug therapy problems (DTPs); however, the clinical utility of PGx information with a clinical decision support tool (CDST) in an MTM setting in identifying DTPs has not been systematically assessed. OBJECTIVE: To assess the clinical utility of an MTM service enhanced by pharmacogenetic test results and a clinical decision support tool...
December 2018: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/30472586/pharmacokinetic-studies-unveiled-the-drug-drug-interaction-between-trans-2-3-5-4-tetrahydroxystilbene-2-o-%C3%AE-d-glucopyranoside-and-emodin-that-may-contribute-to-the-idiosyncratic-hepatotoxicity-of-polygoni-multiflori-radix
#11
Yanchao Xing, Linlin Wang, Chenxi Wang, Youcai Zhang, Yi Zhang, Limin Hu, Xiumei Gao, Lifeng Han, Wenzhi Yang
Polygoni Multiflori Radix (PMR) has been a reputable tonifying traditional Chinese medicine for a long history. However, clinical side effects regarding its idiosyncratic hepatotoxicity are occasionally reported. The containing anthraquinones, particularly emodin, could cause liver injury in both in vitro and in vivo experiments. It is well-known that some compounds could influence other compounds' pharmacokinetic parameters significantly. In this work, the influence of trans-2,3,5,4'-tetrahydroxystilbene-2-O-β-d-glucopyranoside (TSG) on the pharmacokinetic behavior of emodin in rats was evaluated by an ultra-high performance liquid chromatography/triple quadrupole mass spectrometry (UHPLC/MS-MS) approach...
November 16, 2018: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/30464555/the-effects-of-cytochrome-p450-2c19-polymorphism-on-the-metabolism-of-voriconazole-in-vitro
#12
Ren-Ai Xu, Er-Min Gu, Teng-Hui Liu, Qiu-Geng Ou-Yang, Guo-Xin Hu, Jian-Ping Cai
Background: CYP/CYP450 2C19 (CYP2C19) is a highly polymorphic enzyme and exhibits individual differences in metabolic activity. The purpose of this research was mainly to explore the catalytic activities of 30 CYP2C19 variants on the substrate voriconazole in vitro, including 24 novel CYP2C19 variants (2C19.2E-.2H, .2J, .3C, .29-.33, L16F, 35FS, R124Q, R125G, T130M, N231T, M255T, R261W, N277K, S303N, I327T, N403I, and A430V) found in Chinese Han population for the first time. Methods: These CYP2C19 variants were expressed in Spodoptera frugiperda ( Sf ) 21 insect cells using the baculovirus-mediated expression system...
2018: Infection and Drug Resistance
https://www.readbyqxmd.com/read/30459618/metabolism-and-bioactivation-of-corynoline-with-characterization-of-the-glutathione-cysteine-conjugate-and-evaluation-of-its-hepatotoxicity-in-mice
#13
Ruijuan Liu, Fang Zhou, He He, Jingyao Wei, Xin Tian, Li Ding
Corynoline (CRL), an isoquinoline alkaloid, is the major constituent derived from Corydalis bungeana Herba, which is a well-known Chinese herbal medicine widely used in many prescriptions. The purpose of this study was to comprehensively investigate the metabolism and bioactivation of CRL, and identify the CYP450 isoforms involved in reactive ortho -benzoquinone metabolites formation and evaluate its hepatotoxicity in mice. Here, high resolution and triple quadrupole mass spectrometry were used for studying the metabolism of CRL...
2018: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/30457473/effects-of-herbal-formulas-bojungikgi-tang-and-palmijihwang-hwan-on-inflammation-in-raw-264-7-cells-and-the-activities-of-drug-metabolizing-enzymes-in-human-hepatic-microsomes
#14
Seong Eun Jin, Hyekyung Ha, Hyeun-Kyoo Shin
In the present study, Bojungikgi-tang (BJIKT: Buzhongyiqi-tang, Hochuekki-to) and Palmijihwang-hwan (PMJHH: Baweidìhuang-wan, Hachimijio-gan), traditional herbal formulas, investigated anti-inflammatory efficacies in murine macrophage cell line and the influence on the activities of drug-metabolizing enzymes (DMEs). The anti-inflammatory potentials of the herbal formulas were evaluated to inhibit the production of the inflammatory mediators and cytokines and the protein expression of inducible nitric oxide and cyclooxygenase-2 (COX-2) in lipopolysaccharide (LPS)-treated RAW 264...
November 2018: Journal of Medicinal Food
https://www.readbyqxmd.com/read/30428372/bioprinted-3d-primary-human-intestinal-tissues-model-aspects-of-native-physiology-and-adme-tox-functions
#15
Lauran R Madden, Theresa V Nguyen, Salvador Garcia-Mojica, Vishal Shah, Alex V Le, Andrea Peier, Richard Visconti, Eric M Parker, Sharon C Presnell, Deborah G Nguyen, Kelsey N Retting
The human intestinal mucosa is a critical site for absorption, distribution, metabolism, and excretion (ADME)/Tox studies in drug development and is difficult to recapitulate in vitro. Using bioprinting, we generated three-dimensional (3D) intestinal tissue composed of human primary intestinal epithelial cells and myofibroblasts with architecture and function to model the native intestine. The 3D intestinal tissue demonstrates a polarized epithelium with tight junctions and specialized epithelial cell types and expresses functional and inducible CYP450 enzymes...
April 27, 2018: iScience
https://www.readbyqxmd.com/read/30426002/effects-of-digeda-4-decoction-on-the-cyp450-activities-in-rats-using-a-cocktail-method-by-hplc
#16
Dong Zhang, Guo-Dong Wu, Yan-Dong Zhang, Jian-Ping Xu, Hai-Tao Zhen, Min-Hui Li
Digeda-4 decoction is a traditional Mongolian medicine; its effects on cytochrome (CYP) enzymes are still unclear. CYP450 isoenzymes are the main drug metabolic enzymes, and their activities may be induced or inhibited by certain drugs, which lead to drug interactions in clinical use. Effects of Digeda-4 decoction on the activities of CYP450 subtype enzymes CYP1A2, CYP2C9, CYP2E1, CYP2C19, and CYP3A4 in rats were studied by cocktail method, and the pharmacokinetic parameters of five specific probe drugs (theophylline, tolbutamide, chlorzoxazone, omeprazole, and midazolam) were calculated by DAS software; changes of parameters can be used to evaluate the effects of Digeda-4 decoction on enzyme activities...
2018: BioMed Research International
https://www.readbyqxmd.com/read/30425549/-cyp2d6-genotype-can-help-to-predict-effectiveness-and-safety-during-opioid-treatment-for-chronic-low-back-pain-results-from-a-retrospective-study-in-an-italian-cohort
#17
Concetta Dagostino, Massimo Allegri, Valerio Napolioni, Simona D'Agnelli, Elena Bignami, Antonio Mutti, Ron Hn van Schaik
Background: Opioids are widely used for chronic low back pain (CLBP); however, it is still unclear how to predict their effectiveness and safety. Codeine, tramadol and oxycodone are metabolized by CYP/CYP450 2D6 (CYP2D6), a highly polymorphic enzyme linked to allele-specific related differences in metabolic activity. Purpose: CYP2D6 genetic polymorphisms could potentially help to predict the effectiveness and safety of opioid-based drugs in clinical practice, especially in the treatment of CLBP...
2018: Pharmacogenomics and Personalized Medicine
https://www.readbyqxmd.com/read/30423565/mice-deficient-in-cyp4a14-have-an-increased-number-of-goblet-cells-and-attenuated-dextran-sulfate-sodium-induced-colitis
#18
Qingxia Xuan, Yunfeng Zhou, Binbin Tan, Zhongyue Xiao, Shizhen Dong, Faliang Dai, Lei Gao, Tengfei Guo, Pan Chen, Jie Sun, Dandan Feng, Jianjun Jin, Fong-Fong Chu, Qiang Gao
BACKGROUND/AIMS: Cyp4a14 is a member of cytochrome P450 (Cyp450) enzyme superfamily that possesses NADPH monooxygenase activity, which catalyzes omega-hydroxylation of medium-chain fatty acids and arachidonic acid. Study suggests that down-regulation of Cyp4a14 has an anti-inflammatory response in intestine. The present study was to test the function of Cyp4a14 in dextran sulfate sodium (DSS)-induced colitis. METHODS: Female Cyp4a14-knockout (KO) and wild-type (WT) mice were treated with DSS for 6 days to induce colitis...
2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/30400671/possible-role-of-cyp450-generated-omega-3-omega-6-pufa-metabolites-in-the-modulation-of-blood-pressure-and-vascular-function-in-obese-children
#19
Sara Bonafini, Alice Giontella, Angela Tagetti, Denise Marcon, Martina Montagnana, Marco Benati, Rossella Gaudino, Paolo Cavarzere, Mirjam Karber, Michael Rothe, Pietro Minuz, Franco Antonazzi, Claudio Maffeis, Wolf Hagen Schunck, Cristiano Fava
Obesity is often accompanied by metabolic and haemodynamic disorders such as hypertension, even during childhood. Arachidonic acid (AA) is metabolized by cytochrome P450 (CYP450) enzymes to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acid (20-HETE), vasoactive and natriuretic metabolites that contribute to blood pressure (BP) regulation. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) omega-3 polyunsaturated fatty acids may compete with AA for CYP450-dependent bioactive lipid mediator formation...
November 5, 2018: Nutrients
https://www.readbyqxmd.com/read/30392018/the-protection-of-selenium-against-cadmium-induced-mitochondrial-damage-via-the-cytochrome-p450-in-the-livers-of-chicken
#20
Yimei Cong, Qianru Chi, Xiaohua Teng, Shu Li
Cadmium (Cd) is a heavy metal in natural environment and has extreme toxicity. Selenium (Se) has protective effect against heavy metal-induced injury or oxidative stress. Cytochrome P450 (CYP450) enzymes are a family of hemoproteins primarily responsible for detoxification functions. In order to investigate whether CYP450 is related to the damage of livers caused by Cd exposure, we chose forty-eight 28-day-old healthy Hailan cocks for four groups: control group, Se group, Cd group, and Se + Cd group. After 90-day treatment, euthanized for experiment...
November 3, 2018: Biological Trace Element Research
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