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https://www.readbyqxmd.com/read/28541669/effects-of-polychlorinated-biphenyls-pcbs-and-their-hydroxylated-metabolites-oh-pcbs-on-arabidopsis-thaliana
#1
Srishty Subramanian, Jerald L Schnoor, Benoit Van Aken
Plants metabolize polychlorinated biphenyls (PCBs) into hydroxylated derivatives (OH-PCBs), which are sometimes more toxic than the parent PCBs. The objective of this research was to compare the toxicity of a suite of PCBs and OH-PCBs toward the model plant, Arabidopsis thaliana. While parent PCBs and higher-chlorinated OH-PCBs exhibited a low or non-detectable toxicity, lower-chlorinated OH-PCBs significantly inhibited the germination rate and plant growth, with IC50 ranging from 1.6 to 12.0 mg L-1. The transcriptomic response of A...
May 25, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/28513969/effect-of-steady-state-faldaprevir-on-pharmacokinetics-of-atorvastatin-or-rosuvastatin-in-healthy-volunteers-a-prospective-open-label-fixed-sequence-crossover-study
#2
Fenglei Huang, Kristell Marzin, Rüdiger Koenen, Klaus Peter Kammerer, Natalja Strelkowa, Mabrouk Elgadi, Anne-Marie Quinson, Sebastian Haertter
Faldaprevir (FDV) is a potent, orally administered inhibitor of hepatitis C virus protease. It inhibits multiple cytochrome P-450 enzymes and multiple membrane transporters. The objective of this study was to evaluate the effect of steady-state faldaprevir on the pharmacokinetics (PK) of a single dose of atorvastatin or rosuvastatin. In this single-center, open-label, fixed-sequence crossover study, 33 healthy adult male and female volunteers were given either atorvastatin 10 mg (n = 16) or rosuvastatin 10 mg (n = 17) on day 1...
May 17, 2017: Journal of Clinical Pharmacology
https://www.readbyqxmd.com/read/28513222/the-contribution-of-cyp2c-gene-subfamily-involved-in-epoxygenase-pathway-of-arachidonic-acids-metabolism-to-hypertension-susceptibility-in-russian-population
#3
Alexey Polonikov, Marina Bykanova, Irina Ponomarenko, Svetlana Sirotina, Anna Bocharova, Kseniya Vagaytseva, Vadim Stepanov, Mikhail Churnosov, Olga Bushueva, Maria Solodilova, Yaroslav Shvetsov, Vladimir Ivanov
Numerous studies demonstrated an importance of cytochrome P-450 epoxygenase pathway of arachidonic acids metabolism for the pathogenesis of essential hypertension (EH). The present study was designed to investigate whether common single-nucleotide polymorphisms (SNP) of CYP2C gene subfamily such as CYP2C8 (rs7909236 and rs1934953), CYP2C9 (rs9332242), and CYP2C19 (rs4244285) are associated with susceptibility to EH in Russian population. A total of 816 unrelated Russian individuals comprising 425 EH patients and 391 normotensive controls were included into the study...
May 17, 2017: Clinical and Experimental Hypertension: CHE
https://www.readbyqxmd.com/read/28501544/the-dna-methylation-status-alteration-of-two-steroidogenic-genes-in-gonads-of-rare-minnow-after-bisphenol-a-exposure
#4
Ting Zhang, Yan Liu, Hong Chen, Jiancao Gao, Yingying Zhang, Cong Yuan, Zaizhao Wang
Both cytochrome P450c17 (CYP17A1) and P-450 side chain cleavage (CYP11A1) play important roles in steroid biosynthesis. According to our previous studies, bisphenol A (BPA) could regulate the mRNA expression of cyp17a1 and cyp11a1 in rare minnow Gobiocypris rarus. However, the potential mechanism of the regulation is barely understood. In the present study, aiming to explore how BPA affects the mRNA expression of cyp17a1 and cyp11a1 in testes and ovaries of G. rarus, we firstly cloned 340-bp fragment of 5' flanking region of cyp11a1 and then detected the methylation level of CpG loci involved in 5' flanking of cyp11a1 and cyp17a1 and their mRNA expression levels...
May 10, 2017: Comparative Biochemistry and Physiology. Toxicology & Pharmacology: CBP
https://www.readbyqxmd.com/read/28501210/determination-of-tocopherols-and-their-metabolites-by-liquid-chromatography-coupled-with-tandem-mass-spectrometry-in-human-plasma-and-serum
#5
Danilo Giusepponi, Pierangelo Torquato, Desirée Bartolini, Marta Piroddi, Marc Birringer, Stefen Lorkowski, Carmelo Libetta, Gabriele Cruciani, Simone Moretti, Giorgio Saluti, Francesco Galli, Roberta Galarini
Several studies are increasingly underlying the biological role of vitamin E metabolites as bioactive compounds with anti-inflammatory, anti-proliferative and anti-atherogenic activity. A quantitative method for the simultaneous determination in human plasma and serum of vitamin E (α-tocopherol, α-T and γ-tocopherol, γ-T) and its cytochrome P-450 metabolites: 13'-hydroxychromanol (α-13'-OH), 13'-carboxychromanol (α-13'-COOH) and carboxyethyl hydroxychromanols (α-CEHC and γ-CEHC), was developed and validated...
August 1, 2017: Talanta
https://www.readbyqxmd.com/read/28495029/the-pharmacokinetics-of-the-cyp3a-substrate-midazolam-after-steady-state-dosing-of-delafloxacin
#6
Susan K Paulson, Rebecca N Wood-Horrall, Randall Hoover, Megan Quintas, Laura E Lawrence, Sue K Cammarata
PURPOSE: Delafloxacin is a novel anionic fluoroquinolone in Phase III development for the treatment of serious skin infections. The objective of this study was to evaluate the effects of delafloxacin on the pharmacokinetics of midazolam, a cytochrome P450 (CYP) 3A substrate. METHODS: CYP3A activity using midazolam as a probe was assessed before and after multiple doses of delafloxacin to reach steady state. In this nonrandomized, open-label, single-sequence, Phase I study, 22 healthy male and female subjects were administered a single 5-mg oral dose of midazolam on days 1 and 8, with oral delafloxacin 450 mg every 12 hours administered from days 3 to 8...
May 8, 2017: Clinical Therapeutics
https://www.readbyqxmd.com/read/28494841/quercetin-attenuates-benzo-%C3%AE-pyrene-induced-cyp1a-expression
#7
M L Perepechaeva, T A Seredina, Y A Sidorova, E N Pivovarova, A L Markel, V V Lyakhovich, A Y Grishanova
We studied effects of nutrient quercetin on cytochromes' Р450 1А (CYP1A) activities (measured spectrofluorimetrically using 7-ethoxy-resorufin for CYP1A1 and 7-methoxy-resorufin for CYP1A2 as substrates), on mRNA levels (measured by RT-PCR), and on DNA-binding activities (evaluated by an electrophoretic mobility shift assay) of proteins regulating CYP1A expression in untreated and benzo(α)pyrene (BaP)-treated rats. Wistar rats received quercetin, BaP, or both once daily for 1-3 days. Quercetin did not influence CYP1A1 in untreated rats but inhibited BaP-mediated CYP1A induction on the transcriptional level decreasing positive input (AhR functional activity) and increasing negative input (AhRR/ARNT expression and Oct-1 and C/EBP functional activities)...
April 2017: Biomedical and Environmental Sciences: BES
https://www.readbyqxmd.com/read/28492277/association-study-and-expression-analysis-of-cyp4a11-gene-copy-number-variation-in-chinese-cattle
#8
Mingjuan Yang, Jingqiao Lv, Liangzhi Zhang, Mingxun Li, Yang Zhou, Xianyong Lan, Chuzhao Lei, Hong Chen
The identification of copy number variations (CNVs) allow us to explore genomic polymorphisms. In recent years, significant progress in understanding CNVs has been made in studies of human and animals, however, association and expression studies of CNVs are still in the early stage. It was previously reported that the Cytochrome P-450 4A11 (CYP4A11) gene is located within a copy number variable region (CNVR) that encompasses quantitative trait loci (QTLs) for economic traits like meat quality and milk production...
May 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28469395/cytochrome-p-450-1b1-leu432val-polymorphism-does-not-show-association-with-breast-cancer-in-northern-iranian-women-with-a-history-of-infertility
#9
Maryam Ghanbari Andarieh, Ebrahim Zabihi, Dariush Moslemi, Mouloud Agajani Delavar, Mahmoud Haji-Ahmadi, Ali Shabestani Monfared, Seyed Gholam Ali Jorsaraei, Masoumeh Ghasemi, Sedighe Esmaeilzadeh
The Cytochrome P-4501B1 (CYP1B1) Leu432Val polymorphism has been previously shown to be associated with some types of cancer and affects CYP1B1-mediated metabolism of various infertility drugs. To establish the frequency of CYP1B1 Leu432Val polymorphism among women with a history of infertility drug use, we studied the genotypes of 147 patients with breast cancer with a history of infertility and 150 cancer-free, infertile women (control group) in Northern Iran. A polymerase chain reaction-based restriction fragment length polymorphism assay was used to detect GG (Val/Val), CG (Leu/Val), and CC (Leu/Leu) genotype frequencies, which did not vary significantly between the 2 patient groups (P = ...
2017: Biomarker Insights
https://www.readbyqxmd.com/read/28461126/benzo-a-pyrene-induced-dna-damage-associated-with-mutagenesis-in-primary-human-activated-t-lymphocytes
#10
Marie Liamin, Elisa Boutet-Robinet, Emilien L Jamin, Morgane Fernier, Laure Khoury, Benjamin Kopp, Eric Le Ferrec, Julien Vignard, Marc Audebert, Lydie Sparfel
Polycyclic Aromatic Hydrocarbons (PAHs), such as benzo[a]pyrene (B[a]P), are widely distributed environmental contaminants exerting toxic effects such as genotoxicity and carcinogenicity, mainly associated with aryl hydrocarbon receptor (AhR) activation and the subsequent induction of cytochromes P-450 (CYP) 1-metabolizing enzymes. We previously reported an up-regulation of AhR expression and activity in primary cultures of human T lymphocyte by a physiological activation. Despite the suggested link between exposure to PAHs and the risk of lymphoma, the potential of activated human T lymphocytes to metabolize AhR exogenous ligands such as B[a]P and produce DNA damage has not been investigated...
April 28, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28459658/enhanced-oral-bioavailability-of-domperidone-with-piperine-in-male-wistar-rats-involvement-of-cyp3a1-and-p-gp-inhibition
#11
Bhargavi Latha Athukuri, Prasad Neerati
PURPOSE: Domperidone is a commonly used antiemetic drug. The oral bioavailability of domperidone is very low due to its rapid first pass metabolism in the intestine and liver. Piperine, the main alkaloid present in black pepper has been reported to show inhibitory effects on Cytochrome P-450 (CYP-450) enzymes and P-glycoprotein (P-gp). In the present study we investigated the effect of piperine pretreatment on the intestinal transport and oral bioavailability of domperidone in male Wistar rats...
2017: Journal of Pharmacy & Pharmaceutical Sciences: a Publication of the Canadian Society for Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28412920/neuropsychiatric-and-general-interactions-of-natural-and-synthetic-cannabinoids-with-drugs-of-abuse-and-medicines
#12
Ana Lucia Arellano, Esther Papaseit, Anna Romaguera, Marta Torrens, Magi Farré
Cannabis is the most widely used illicit drug. The two most important natural cannabinoids are delta-9-tetrahydrocannabinol (THC) and cannabidiol (CBD). The THC content of cannabis has been increasing during the last years and recently appeared in the market a series of synthetic cannabinoids with potent agonist activity. Recreational users frequently combine cannabis with other drugs of abuse as alcohol, amphetamines and derivatives, nicotine and cocaine. In addition these subjects can be taking medicines for acute and chronic medical conditions...
April 13, 2017: CNS & Neurological Disorders Drug Targets
https://www.readbyqxmd.com/read/28404946/cyp-genes-in-osteosarcoma-their-role-in-tumorigenesis-pulmonary-metastatic-microenvironment-and-treatment-response
#13
Alini Trujillo-Paolillo, Francine Tesser-Gamba, Antonio Sergio Petrilli, Maria Teresa de Seixas Alves, Reynaldo Jesus Garcia Filho, Renato de Oliveira, Silvia Regina Caminada de Toledo
Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. The present study investigated the expression of Cytochrome P-450 (CYP) genes: CYP1A2, CYP3A4 and CYP3A5 by qRT-PCR in 135 specimens obtained from OS patients, including biopsy (pre-chemotherapy), tumor resected in surgery (post-chemotherapy), adjacent bone to tumor (nonmalignant tissue), pulmonary metastasis and adjacent lung to metastasis (nonmalignant tissue). Normal bone and normal lung tissues were used as control. We also investigated in five OS cell lines the modulation of CYPs expression by cisplatin, doxorubicin and methotrexate...
March 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28377720/curcumin-successfully-inhibited-the-computationally-identified-cyp2a6-enzyme-mediated-bioactivation-of-aflatoxin-b1-in-arbor-acres-broiler
#14
Ishfaq Muhammad, Xiaoqi Sun, He Wang, Wei Li, Xinghe Wang, Ping Cheng, Sihong Li, Xiuying Zhang, Sattar Hamid
Cytochrome P450 enzymes are often responsible for the toxic and carcinogenic effects of toxicants, such as aflatoxin B1 (AFB1). The human hepatic CYP2A6 enzyme mediates the oxidative metabolism of several procarcinogens. In this study, we characterized a partial sequence of CYP2A6 gene from Arbor Acres (AA) broiler and studied its role in AFB1 bioactivation. Moreover, the effect of curcumin on CYP2A6 is illustrated. Six groups of AA broiler were treated for 28 days including the control group (fed only basal diet), curcumin alone-treated group (450 mg/kg feed), the group fed AFB1-contaminated feed (5 mg/kg feed) plus the low (150 mg), medium (300 mg) or high (450 mg) of curcumin, and the group fed AFB1-contaminated diet alone (5 mg/kg feed)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28377716/human-cytochrome-p450-3a4-as-a-biocatalyst-effects-of-the-engineered-linker-in-modulation-of-coupling-efficiency-in-3a4-bmr-chimeras
#15
Danilo Degregorio, Serena D'Avino, Silvia Castrignanò, Giovanna Di Nardo, Sheila J Sadeghi, Gianluca Catucci, Gianfranco Gilardi
Human liver cytochrome P450 3A4 is the main enzyme involved in drug metabolism. This makes it an attractive target for biocatalytic applications, such as the synthesis of pharmaceuticals and drug metabolites. However, its poor solubility, stability and low coupling have limited its application in the biotechnological context. We previously demonstrated that the solubility of P450 3A4 can be increased by creating fusion proteins between the reductase from Bacillus megaterium BM3 (BMR) and the N-terminally modified P450 3A4 (3A4-BMR)...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28367588/effect-of-long-term-in-vitro-lithium-exposure-on-mrna-levels-of-claudin-3-cyp1a1-abcg2-and-gstm3-genes-in-the-hcmec-d3-human-brain-endothelial-cell-line
#16
Ramzi Shawahna, Kayathiri Ganeshamoorthy, Luo Huilong, Jean-Michel Scherrmann, Pierre-Olivier Couraud, Xavier Declèves
BACKGROUND AND OBJECTIVES: Lithium chloride (LiCl) has been shown to improve the tightness of brain endothelial cell monolayers in vitro by inhibition of the GSK-3β enzyme, activation of the Wnt/beta-catenin pathway and regulation of tight junction (TJ) protein expression. However, the effect of LiCl on the drug transporters and drug-metabolizing enzymes has not been addressed so far. The hCMEC/D3 cell line is a validated in vitro BBB model expressing transporters and drug-metabolizing enzymes (phase 1 and 2)...
April 3, 2017: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/28346481/edaravone-protects-against-hyperosmolarity-induced-oxidative-stress-and-apoptosis-in-primary-human-corneal-epithelial-cells
#17
Yanwei Li, Haifeng Liu, Wei Zeng, Jing Wei
An increase in the osmolarity of tears induced by excessive evaporation of the aqueous tear phase is a major pathological mechanism behind dry eye. Exposure of epithelial cells on the surface of the human eye to hyperosmolarity leads to oxidative stress, mitochondrial dysfunction, and apoptosis. Edaravone, a hydroxyl radical scavenging agent, is clinically used to reduce neuronal damage following ischemic stroke. In this study, we found that treatment with hyperosmotic media at 400 and 450 mOsM increased the levels of ROS and mitochondrial oxidative damage, which were ameliorated by edaravone treatment in a dose-dependent manner...
2017: PloS One
https://www.readbyqxmd.com/read/28322174/acanthocotyle-gurgesiella-n-sp-monogenea-acanthocotylidae-from-the-deep-sea-skate-gurgesiella-furvescens-rajidae-in-the-south-eastern-pacific
#18
L A Ñacari, F A Sepulveda, R Escribano, M E Oliva
Little is known about the diversity of parasites of the deep-sea fish of the world's oceans. Here, a new species of monogenean parasite of the deep-sea skate Gurgesiella furvescens is described. Specimens of parasites were obtained from the skin of two specimens of the dusky finless skate, G. furvescens (Rajidae), in the vicinity of Valparaiso (33°S, 72°W), central Chile, from midwater trawl fishing at depths of 350-450 m. Both morphological and molecular analyses were conducted to provide a full description of the new species, named Acanthocotyle gurgesiella...
March 21, 2017: Journal of Helminthology
https://www.readbyqxmd.com/read/28275327/insecticide-resistance-and-cytochrome-p450-activation-in-unfed-and-blood-fed-laboratory-and-field-populations-of-culex-pipiens-pallens
#19
Kyu-Sik Chang, Heung-Chul Kim, Terry A Klein, Young Ran Ju
Understanding the mechanisms of insecticide resistance to vector mosquitoes is critical for the implementation of effective control measures. A nulliparous susceptible Culex pipiens pallens (KSCP) laboratory colony and two field strains from Paju (PAJ) and Jeonju (JEO) Korea were evaluated for susceptibility to five pesticides by microapplication techniques. Unfed PAJ and JEO females demonstrated increased resistance compared to unfed KSCP females, respectively. While blood-fed KSCP females demonstrated <10-fold decreased susceptibility to pesticides compared to unfed KSCP females, blood-fed PAJ and JEO females demonstrated 25...
2017: Journal of Pest Science
https://www.readbyqxmd.com/read/28250275/optimization-of-albumin-secretion-and-metabolic-activity-of-cytochrome-p450-1a1-of-human-hepatoblastoma-hepg2-cells-in-multicellular-spheroids-by-controlling-spheroid-size
#20
Tomoko Nishikawa, Yutaro Tanaka, Makiya Nishikawa, Yuka Ogino, Kosuke Kusamori, Narumi Mizuno, Yuya Mizukami, Kazunori Shimizu, Satoshi Konishi, Yuki Takahashi, Yoshinobu Takakura
Multicellular spheroids are useful as three-dimensional cell culture systems and for cell-based therapies. Their successful application requires an understanding of the consequences of spheroid size for cellular functions. In the present study, we prepared multicellular spheroids of different sizes using the human hepatoblastoma HepG2 cells, as hepatocytes are frequently used for in vitro drug screening and cell-based therapy. Precise polydimethylsiloxane-based microwells with widths of 360, 450, 560, and 770 µm were fabricated using a micromolding technique...
2017: Biological & Pharmaceutical Bulletin
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