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https://www.readbyqxmd.com/read/28551025/cytochrome-p450-derived-eicosanoids-and-heart-function
#1
REVIEW
K Lockhart Jamieson, Tomoko Endo, Ahmed M Darwesh, Victor Samokhvalov, John M Seubert
The cytochrome P450 monooxygenase system (CYP) is a multigene superfamily of enzymes, which are important in the metabolism foreign and endogenous compounds. CYP isoforms metabolize a number of n-3 and n-6 polyunsaturated fatty acids (PUFA), including linoleic acid (18:2n6, LA), arachidonic acid (20:4n6, AA), ecosapentaenoic acid (20:5n3, EPA) and docosahexaenoic acid (22:6n3, DHA) into bioactive lipid mediators, termed eicosanoids. CYP-derived eicosanoids have numerous effects toward physiological and pathophysiological events within the body, which depends on the type, quantity and timing of metabolites produced...
May 24, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28550179/cyp2c44-gene-disruption-is-associated-with-increased-hematopoietic-stem-cells-implication-in-chronic-hypoxia-induced-pulmonary-hypertension
#2
Ryota Hashimoto, Sachindra Raj Joshi, Houli Jiang, Jorge H Capdevila, Ivan F McMurtry, Michal Laniado Schwartzman, Sachin A Gupte
We have recently demonstrated that disruption of the murine cytochrome P450 2c44 gene exacerbates chronic hypoxia-induced pulmonary artery remodeling and hypertension in mice. Subsequently, we serendipitously found that Cyp2c44 gene disruption also increases hematopoietic stem cell (HSC) number in bone marrow and blood. Therefore, the objective of this study was to investigate whether Cyp2c44 disruption regulates HSC phenotype and whether increases in differentiated HSCs contribute to chronic hypoxia-induced remodeling of pulmonary arteries...
May 26, 2017: American Journal of Physiology. Heart and Circulatory Physiology
https://www.readbyqxmd.com/read/28546638/effects-of-obesity-on-liver-cytochromes-p450-in-various-animal-models
#3
Veronika Tomankova, Pavel Anzenbacher, Eva Anzenbacherova
The prevalence of obesity and other obesity-related diseases is increasing worldwide. Obesity is a disease characterized by increased body weight, or a condition resulting from excessive accumulation of body fat. Due to increased body fat deposits, obesity has also been associated with increased mortality resulting from higher incidence rates of hypertension, diabetes, or various types of cancer, such as breast, colorectal, cervical and prostate cancer. Physiological changes associated with obesity are likely to result in altered drug biotransformation...
May 25, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28546420/alterations-of-histone-modifications-contribute-to-pregnane-x-receptor-mediated-induction-of-cyp3a4-by-rifampicin
#4
Liang Yan, Yiting Wang, Jingyang Liu, Yali Nie, Xiaobo Zhong, Quancheng Kan, Lirong Zhang
Cytochrome P450 3A4 (CYP3A4) is one of the major drug-metabolizing enzymes in human and is responsible for the metabolism of 60% of the clinically used drugs. Many drugs are able to induce the expression of CYP3A4, which usually causes drug-drug interactions and adverse drug reactions. This study aims to explore the role of histone modifications in rifampicin-induced expression of CYP3A4 in LS174T cells. We found that the induction of CYP3A4 mRNA by rifampicin in LS174T cells was associated with increased levels of histone H3 lysine 4 trimethylation (H3K4me3) and H3 acetylation and a decreased level of histone H3 lysine 27 trimethylation (H3K27me3) in the CYP3A4 promoter...
May 25, 2017: Molecular Pharmacology
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#5
Enas M Moustafa, Marwa Abdelhameed Mohamed, Noura M Thabet
Purpose: Tumor growth and metastasis depend on angiogenesis; therefore, efforts are being made to develop specific angiogenic inhibitors. Gallium (Ga) is the second most common metal ion, after platinum, used in cancer treatment. Its activities are numerous and various. In the present study, we aimed to investigate the effect of Ga on brain metastasis arising from hepatocellular carcinoma (HCC). Materials and methods: Forty experimental rats (divided into 4 groups) received diethylnitrosamine (DEN) at a dose (20 mg/kg...
April 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28543984/cycle-affects-imidacloprid-efficiency-by-mediating-cytochrome-p450-expression-in-the-brown-planthopper-nilaparvata-lugens
#6
K Kang, P Yang, R Pang, L Yue, W Zhang
Circadian clocks influence most behaviours and physiological activities in animals, including daily fluctuations in metabolism. However, how the clock gene cycle influences insects' responses to pesticides has rarely been reported. Here, we provide evidence that cycle affects imidacloprid efficacy by mediating the expression of cytochrome P450 genes in the brown planthopper (BPH) Nilaparvata lugens, a serious insect pest of rice. Survival bioassays showed that the susceptibility of BPH adults to imidacloprid differed significantly between the two time points tested [Zeitgeber Time 8 (ZT8) and ZT4]...
May 23, 2017: Insect Molecular Biology
https://www.readbyqxmd.com/read/28543042/the-ntcp-inhibitor-myrcludex-b-effects-on-bile-acid-disposition-and-tenofovir-pharmacokinetics
#7
Antje Blank, Annette Eidam, Mathias Haag, Nicolas Hohmann, Jürgen Burhenne, Matthias Schwab, Stan F J van de Graaf, Markus R Meyer, Hans H Maurer, Katrin Meier, Johanna Weiss, Thomas Bruckner, Alexander Alexandrov, Stephan Urban, Gerd Mikus, Walter E Haefeli
Myrcludex B acts as a hepatitis B and D virus entry inhibitor blocking the sodium taurocholate co-transporting polypeptide (SLC10A1). We investigated effects of myrcludex B on plasma bile acid disposition, tenofovir pharmacokinetics, and perpetrator characteristics on cytochrome P450 (CYP) 3A. Twelve healthy volunteers received 300 mg tenofovir disoproxil fumarate orally and 10 mg subcutaneous myrcludex B. Myrcludex B increased total plasma bile acid exposure 18.2-fold without signs of cholestasis. The rise in conjugated bile acids was up to 123-fold (taurocholic acid)...
May 24, 2017: Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28542511/association-of-cyp2a6-activity-with-lung-cancer-incidence-in-smokers-the-multiethnic-cohort-study
#8
Sungshim L Park, Sharon E Murphy, Lynne R Wilkens, Daniel O Stram, Stephen S Hecht, Loïc Le Marchand
While smoking is the primary cause of lung cancer, only 11-24% of smokers develop the malignancy over their lifetime. The primary addictive agent in tobacco smoke is nicotine and variation in nicotine metabolism may influence the smoking levels of an individual. Therefore, inter-individual variation in lung cancer risk among smokers may be due in part to differences in the activity of enzymes involved in nicotine metabolism. In most smokers, cytochrome P450 2A6 (CYP2A6)-catalyzed C-oxidation accounts for >75% of nicotine metabolism, and the activity of this enzyme has been shown to correlate with the amount of nicotine and carcinogens drawn from cigarettes...
2017: PloS One
https://www.readbyqxmd.com/read/28542000/ketamine-and-etomidate-down-regulate-the-hypothalamic-pituitary-adrenal-axis-in-an-endotoxemic-mouse-model
#9
Emmanuel Besnier, Thomas Clavier, Marie-Christine Tonon, Jean Selim, Antoine Lefevre-Scelles, Fabrice Morin, Fabienne Tamion, Bertrand Dureuil, Hélène Castel, Vincent Compere
BACKGROUND: We compared the effects of etomidate and ketamine on the hypothalamic-pituitary-adrenal axis during sepsis. METHODS: Mice (n = 5/group) were injected intraperitoneally with lipopolysaccharide (10 mg/kg) and 6 h later randomized to receive ketamine (100 mg/kg), etomidate (30 mg/kg), or saline. At two time points (12 and 48 h), messenger RNA levels of hypothalamic corticotropin-releasing hormone, pituitary proopiomelanocortin, and four adrenal enzymes (P450 side-chain cleavage, 3β-hydroxysteroid deshydrogenase, 21-hydroxylase, and 11β-hydroxylase) were measured by in situ hybridization (results are presented as optical density), and plasma levels of corticosterone and adrenocorticotropin hormones were measured by enzyme-linked immunosorbent assay (mean ± SD)...
May 25, 2017: Anesthesiology
https://www.readbyqxmd.com/read/28541629/adult-granulosa-cell-tumors-of-the-ovary-a-retrospective-study-of-30-cases-with-respect-to-the-expression-of-steroid-synthesis-enzymes
#10
Sachiko Kitamura, Kaoru Abiko, Noriomi Matsumura, Hidekatsu Nakai, Yumiko Akimoto, Hirotoshi Tanimoto, Ikuo Konishi
OBJECTIVE: Some, but not all, granulosa cell tumors are characterized by estrogen production. This study was designed to determine whether there are clinical or pathological variations in granulosa cell tumors in relation to the expression of sex steroid synthesis enzymes. METHODS: Clinical symptoms, serum hormonal values, and histology of 30 granulosa cell tumor patients who underwent surgery between 2002 and 2014 were retrospectively reviewed. RESULTS: Most patients presented with abnormal genital bleeding including abnormal menstrual cycles...
July 2017: Journal of Gynecologic Oncology
https://www.readbyqxmd.com/read/28540639/exploiting-pharmacokinetic-models-of-tamoxifen-and-endoxifen-to-identify-factors-causing-subtherapeutic-concentrations-in-breast-cancer-patients
#11
Lena Klopp-Schulze, Markus Joerger, Sebastian G Wicha, Rob Ter Heine, Chantal Csajka, Zinnia P Parra-Guillen, Charlotte Kloft
BACKGROUND AND OBJECTIVES: A better understanding of the highly variable pharmacokinetics (PK) of tamoxifen and its active metabolite endoxifen in breast cancer patients is crucial to support individualised treatment. This study used a modelling and simulation approach to quantitatively assess the influence of cytochrome P450 (CYP) 2D6 activity and other relevant factors on tamoxifen and endoxifen PK to identify subgroups at risk for subtherapeutic endoxifen concentrations. METHODS: Simulations were performed using two previously published PK models jointly describing tamoxifen and endoxifen with CYP2D6 and CYP3A4/5 enzyme activities implemented as covariates...
May 24, 2017: Clinical Pharmacokinetics
https://www.readbyqxmd.com/read/28540569/altered-purinergic-signaling-in-uridine-adenosine-tetraphosphate-induced-coronary-relaxation-in-swine-with-metabolic-derangement
#12
Zhichao Zhou, Oana Sorop, Vincent J de Beer, Ilkka Heinonen, Caroline Cheng, A H Jan Danser, Dirk J Duncker, Daphne Merkus
We previously demonstrated that uridine adenosine tetraphosphate (Up4A) induces potent and partially endothelium-dependent relaxation in the healthy porcine coronary microvasculature. We subsequently showed that Up4A-induced porcine coronary relaxation was impaired via downregulation of P1 receptors after myocardial infarction. In view of the deleterious effect of metabolic derangement on vascular function, we hypothesized that the coronary vasodilator response to Up4A is impaired in metabolic derangement, and that the involvement of purinergic receptor subtypes and endothelium-derived vasoactive factors (EDVFs) is altered...
May 24, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28539725/inhibition-of-cytochrome-p450-cyp3a4-activity-by-extracts-from-57-plants-used-in-traditional-chinese-medicine-tcm
#13
Mohamed L Ashour, Fadia S Youssef, Haidy A Gad, Michael Wink
BACKGROUND: Herbal medicine is widely used all over the world for treating various health disorders. It is employed either alone or in combination with synthetic drugs or plants to be more effective. OBJECTIVE: The assessment of the effect of both water and methanol extracts of 57 widely used plants from Traditional Chinese Medicine (TCM) against the main phase I metabolizing enzyme CYP3A4 in vitro for the first time. MATERIALS AND METHODS: The inhibition of cytochrome P450 activity was evaluated using a luminescence assay...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539714/evaluation-of-herb-drug-interactions-of-hovenia-dulcis-fruit-extracts
#14
Jong Suk Park, Shaheed Ur Rehman, In Sook Kim, Min Sun Choi, Chun-Soo Na, Hye Hyun Yoo
BACKGROUND: Hovenia dulcis (Rhamnaceae) fruits are popularly used as herbal medicines or dietary supplements in Asian countries due to functions such as liver protection and detoxification from alcohol poisoning. Accordingly, it is very likely for dietary supplemental products, including H. dulcis fruit extracts, to be taken with prescription drugs. OBJECTIVE: In this study, possible food-drug interactions involving H. dulcis fruit extracts were evaluated based on the inhibition of cytochrome P450 (CYP) enzyme activity...
April 2017: Pharmacognosy Magazine
https://www.readbyqxmd.com/read/28539365/functional-analysis-of-human-cytochrome-p450-21a2-variants-involved-in-congenital-adrenal-hyperplasia
#15
Chunxue Wang, Pradeep S Pallan, Wei Zhang, Li Lei, Francis K Yoshimoto, Michael R Waterman, Martin Egli, F Peter Guengerich
Cytochrome P450 (P450, CYP) 21A2 is the major steroid 21-hydroxylase, converting progesterone to 11-deoxycorticosterone and 17α-hydroxy(OH)progesterone to 11-deoxycortisol. More than 100 CYP21A2 variants give rise to congenital adrenal hyperplasia (CAH). We previously reported a structure of wild-type (WT) human P450 21A2 with bound progesterone and now present a structure bound to the other substrate (17α-OH progesterone). We found that the 17α-OH progesterone- and progesterone-bound complex structures are highly similar, with only some minor differences in surface loop regions...
May 24, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28539103/possible-oxcarbazepine-inductive-effects-on-aripiprazole-metabolism-a-case-report
#16
Ian R McGrane, Joshua G Loveland, Jose de Leon
Oxcarbazepine is a cytochrome P450 (CYP) 3A4 inducer, which is structurally similar to carbamazepine. Although lacking Food and Drug Administration approval, oxcarbazepine is sometimes prescribed to treat aggressive behavior in youth with autism spectrum disorder (ASD). These youths may also be taking second-generation antipsychotics, some of which are substrates of the CYP3A4 metabolic pathway. The combination of these medications may result in decreased serum antipsychotic concentrations, potentially reducing effectiveness...
January 1, 2017: Journal of Pharmacy Practice
https://www.readbyqxmd.com/read/28538665/molecular-basis-of-alcohol-related-gastric-and-colon-cancer
#17
REVIEW
Hye-Kyung Na, Ja Young Lee
Many meta-analysis, large cohort studies, and experimental studies suggest that chronic alcohol consumption increases the risk of gastric and colon cancer. Ethanol is metabolized by alcohol dehydrogenases (ADH), catalase or cytochrome P450 2E1 (CYP2E1) to acetaldehyde, which is then further oxidized to acetate by aldehyde dehydrogenase (ALDH). Acetaldehyde has been classified by the International Agency for Research on Cancer (IARC) as a Group 1 carcinogen to humans. The acetaldehyde level in the stomach and colon is locally influenced by gastric colonization by Helicobacter pylori or colonic microbes, as well as polymorphisms in the genes encoding tissue alcohol metabolizing enzymes, especially ALDH2...
May 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28537742/correlating-the-para-substituent-effects-on-ru-ii-polypyridine-photophysical-properties-and-on-the-corresponding-hybrid-p450-bm3-enzymes-photocatalytic-activity
#18
Hadil Shalan, Alexander Colbert, Thanh Truc Nguyen, Mallory Kato, Lionel Cheruzel
Ru(II)-diimine complexes covalently attached near the heme active site of P450 BM3 enzymes have been used to rapidly inject electrons and drive selective C-H functionalization upon visible light irradiation. Herein, we have generated a series of hybrid P450 BM3 enzymes containing a photosensitizer of general formula [Ru(4,4'-X2bpy)2(PhenA)](2+) where X = Cl, H, tBu, Me OPhe, OMe, or NMe2, bpy = 2,2'-bipyridine, and PhenA = 5-acetamido-1,10-phenanthroline. We then probed the effect of electron-withdrawing and -donating groups at the para position of the 4,4'-X2bpy ligands on the corresponding hybrid enzymes photocatalytic activity...
May 24, 2017: Inorganic Chemistry
https://www.readbyqxmd.com/read/28537227/association-of-cyp17a1-genetic-polymorphisms-and-susceptibility-to-essential-hypertension-in-the-southwest-han-chinese-population
#19
Qian Li, Tangxin Gao, Yuncang Yuan, Yanrui Wu, Qionglin Huang, Fei Xie, Pengzhan Ran, Lijuan Sun, Chunjie Xiao
BACKGROUND The CYP17A1 gene encodes for cytochrome P450 enzyme CYP17A1, which is involved with the steroidogenic pathway including mineralocorticoids. The CYP17A1 polymorphisms might affect enzyme activity, then leading to a state of mineralocorticoid 11-deoxycorticosterone excess characterized by hypertension, suppressed plasma renin activity, and low aldosterone concentrations. The aim of this study was to investigate the contribution of CYP17A1 polymorphisms in inducing the susceptibility to essential hypertension among the Southwest Han Chinese population...
May 24, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28536437/monocrotophos-pesticide-affects-synthesis-and-conversion-of-sex-steroids-through-multiple-targets-in-male-goldfish-carassius-auratus
#20
Hua Tian, Yang Sun, Hui Wang, Xin Bing, Wei Wang, Shaoguo Ru
Monocrotophos (MCP) is an organophosphorus pesticide that is median-toxic to fish. MCP pesticide resulted in an increase of 17 beta estradiol following a decrease in testosterone in male goldfish (Carassius auratus). To fully understand the mechanism of MCP pesticide that causes the imbalance between male and female hormones, we determined the levels of plasma cholesterol, spermatic steroidogenic acute regulatory protein mRNA, steroidogenesis enzyme mRNA, plasma sex hormone synthesis intermediates, and effectual hormones in male goldfish exposed to MCP pesticide at nominal concentrations of 0...
May 23, 2017: Scientific Reports
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