keyword
MENU ▼
Read by QxMD icon Read
search

Cytochrome P450

keyword
https://www.readbyqxmd.com/read/29782898/incorporation-of-absorption-and-metabolism-into-liver-toxicity-prediction-for-phytochemicals-a-tiered-in-silico-qsar-approach
#1
Yitong Liu
An increased use of herbal dietary supplements has been associated with adverse liver effects such as elevated serum enzymes and liver failure. The safety assessment for herbal dietary supplements is challenging since they often contain complex mixtures of phytochemicals, most of which have unknown pharmacokinetic and toxicological properties. Rapid tools are needed to evaluate large numbers of phytochemicals for potential liver toxicity. The current study demonstrates a tiered approach combining identification of phytochemicals in liver toxic botanicals, followed by in silico quantitative structure-activity relationship (QSAR) evaluation of these phytochemicals for absorption (e...
May 18, 2018: Food and Chemical Toxicology
https://www.readbyqxmd.com/read/29781479/substrate-mediated-redox-partner-selectivity-of-cytochrome-p450
#2
Katherine A Gentry, Meng Zhang, Sang-Choul Im, Lucy Waskell, Ayyalusamy Ramamoorthy
Investigating the interplay between cytochrome-P450 and its redox partners (CPR and cytochrome-b5) is vital for understanding the metabolism of most hydrophobic drugs. Dynamic structural interactions with the ternary complex, with and without substrates, captured by NMR reveal a gating mechanism for redox partners to promote P450 function.
May 21, 2018: Chemical Communications: Chem Comm
https://www.readbyqxmd.com/read/29780235/the-cytochrome-p450-isoenzyme-and-some-new-opportunities-for-the-prediction-of-negative-drug-interaction-in-vivo
#3
REVIEW
Dmitrij A Sychev, Ghulam Md Ashraf, Andrey A Svistunov, Maksim L Maksimov, Vadim V Tarasov, Vladimir N Chubarev, Vitalij A Otdelenov, Natal'ja P Denisenko, George E Barreto, Gjumrakch Aliev
Cytochrome (CYP) 450 isoenzymes are the basic enzymes involved in Phase I biotransformation. The most important role in biotransformation belongs to CYP3A4, CYP2D6, CYP2C9, CYP2C19 and CYP1A2. Inhibition and induction of CYP isoenzymes caused by drugs are important and clinically relevant pharmacokinetic mechanisms of drug interaction. Investigation of the activity of CYP isoenzymes by using phenotyping methods (such as the determination of the concentration of specific substrates and metabolites in biological fluids) during drug administration provides the prediction of negative side effects caused by drug interaction...
2018: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/29779665/assaying-oxidative-coupling-activity-of-cyp450-enzymes
#4
Vinayak Agarwal
Cytochrome P450 (CYP450) enzymes are ubiquitous catalysts in natural product biosynthetic schemes where they catalyze numerous different transformations using radical intermediates. In this protocol, we describe procedures to assay the activity of a marine bacterial CYP450 enzyme Bmp7 which catalyzes the oxidative radical coupling of polyhalogenated aromatic substrates. The broad substrate tolerance of Bmp7, together with rearrangements of the aryl radical intermediates leads to a large number of products to be generated by the enzymatic action of Bmp7...
2018: Methods in Enzymology
https://www.readbyqxmd.com/read/29779438/metabolism-of-deltamethrin-and-cis-and-trans-permethrin-by-human-expressed-cytochrome-p450-and-carboxylesterase-enzymes
#5
Laura Hedges, Susan Brown, A Kenneth MacLeod, Audrey Vardy, Edward Doyle, Gina Song, Marjory Moreau, Miyoung Yoon, Thomas G Osimitz, Brian G Lake
1. The metabolism of the pyrethroids deltamethrin (DLM), cis-permethrin (CPM) and trans-permethrin (TPM) was studied in human expressed cytochrome P450 (CYP) and carboxylesterase (CES) enzymes. 2. DLM, CPM and TPM were metabolised by human CYP2B6 and CYP2C19, with the highest apparent intrinsic clearance (CLint ) values for pyrethroid metabolism being observed with CYP2C19. Other CYP enzymes contributing to the metabolism of one or more of the three pyrethroids were CYP1A2, CYP2C8, CYP2C9*1, CYP2D6*1, CYP3A4 and CYP3A5...
May 21, 2018: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/29779093/pharmacokinetics-of-the-novel-selective-non-steroidal-mineralocorticoid-receptor-antagonist-finerenone-in-healthy-volunteers-results-from-an-absolute-bioavailability-study-and-drug-drug-interaction-studies-in-vitro-and-in-vivo
#6
Roland Heinig, Michael Gerisch, Anna Engelen, Johannes Nagelschmitz, Stephanie Loewen
BACKGROUND AND OBJECTIVES: Finerenone is a selective, non-steroidal mineralocorticoid receptor antagonist. In vivo and in vitro studies were performed to assess absolute bioavailability of finerenone, the effect of metabolic enzyme inhibitors on the pharmacokinetics of finerenone and its metabolites, the quantitative contribution of the involved enzymes cytochrome P450 (CYP) 3A4 and CYP2C8 and the relevance of gut wall versus liver metabolism. METHODS: The pharmacokinetics, safety and tolerability of finerenone (1...
May 19, 2018: European Journal of Drug Metabolism and Pharmacokinetics
https://www.readbyqxmd.com/read/29778238/interplay-between-estrogen-related-receptors-and-steroidogenesis-controlling-molecules-in-adrenals-in-vivo-and-in-vitro-study
#7
A Pacwa, E Gorowska-Wojtowicz, A Ptak, P Pawlicki, A Milon, M Sekula, K Lesniak, B Bilinska, A Hejmej, M Kotula-Balak
Estrogen-related receptors (ERRs) α, β and γ appear to be novel molecules implicated in estrogen signaling. We blocked and activated ERRs in mouse (C57BL/6) adrenals and adrenocortical cells (H295R) using pharmacological agents XCT 790 (ERRα antagonist) and DY131 (ERRβ/γ agonist), respectively. Mice were injected with XCT 790 or DY131 (5 μg/kg bw) while cells were exposed to XCT 790 or DY131 (0.5 μg/L). Irrespectively of the agent used, changes in adrenocortical cell morphology along with changes in lutropin, cholesterol levels and estrogen production were found...
May 16, 2018: Acta Histochemica
https://www.readbyqxmd.com/read/29778080/atrazine-xenobiotic-nuclear-receptor-interactions-induce-cardiac-inflammation-and-endoplasmic-reticulum-stress-in-quail-coturnix-coturnix-coturnix
#8
Xue-Nan Li, Yu-Zhu Zuo, Lei Qin, Wei Liu, Yan-Hua Li, Jin-Long Li
Atrazine (ATR) is one of the most extensively used herbicide that eventually leaches into groundwater and surface water from agricultural areas. Exposure to ATR does harm to the health of human and animals, especially the heart. However, ATR exposure caused cardiotoxicity in bird remains unclear. To evaluate ATR-exerted potential cardiotoxicity in heart, quail were exposed with 0, 50, 250, and 500 mg/kg BW/day ATR by gavage treatment for 45 days. Cardiac histopathological alternation was observed in ATR-induced quail...
May 9, 2018: Chemosphere
https://www.readbyqxmd.com/read/29777725/strain-related-differences-in-mouse-lung-gene-expression-over-a-two-year-period-of-inhalation-exposure-to-styrene-relevance-to-human-risk-assessment
#9
Melvin E Andersen, George Cruzan, Michael B Black, Salil N Pendse, Darol E Dodd, James S Bus, Satinder S Sarang, Marcy I Banton, Robbie Waites, Debra B Layko, Patrick D McMullen
Both CD-1 and C57BL/6 wildtype (C57BL/6-WT) mice show equivalent short-term lung toxicity from exposures to styrene, while long-term tumor responses are greater in CD-1 mice. We analyzed lung gene expression from styrene exposures lasting from 1-day to 2-years in male mice from these two strains, including a Cyp2f2(-/-) knockout (C57BL/6-KO) and a Cyp2F1/2A13/2B6 transgenic mouse (C57BL/6-TG). With short term exposures (1-day to 1-week), CD-1 and C57BL/6-WT mice had thousands of differentially expressed genes (DEGs), consistent with changes in pathways for cell proliferation, cellular lipid metabolism, DNA-replication and inflammation...
May 16, 2018: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/29777680/assay-for-abscisic-acid-8-hydroxylase-activity-of-cloned-plant-cytochrome-p450-oxidases-in-saccharomyces-cerevisiae
#10
Stella Eggels, Viktoriya Avramova, Chris-Carolin Schön, Brigitte Poppenberger, Wilfried Rozhon
The plant hormone abscisic acid (ABA) regulates many processes, including response to drought, seed dormancy and abscission of leaves and fruits. For maintenance of ABA homeostasis, catabolism of ABA by 8'-hydroxylation and subsequent cyclisation to phaseic acid (PA) is crucial. However, detection of ABA 8'-hydroxylation activity is tedious. We present a simple and rapid method for detection of ABA 8'-hydroxylase activity by cloning cDNAs of interest and expressing the respective protein in yeast. Upon addition of ABA, PA is formed and subsequently quantified in the yeast cell culture supernatant by heart cutting 2D-HPLC or GC-MS...
May 16, 2018: Analytical Biochemistry
https://www.readbyqxmd.com/read/29775944/alterations-of-cytochrome-p450-and-the-occurrence-of-persistent-organic-pollutants-in-tilapia-caged-in-the-reservoirs-of-the-igua%C3%A3-u-river
#11
F Y Yamamoto, G D Diamante, M S Santana, D R Santos, R Bombardeli, C C Martins, C A Oliveira Ribeiro, D Schlenk
Environmental chemicals originating from human activities, such as persistent organic pollutants (POPs), may interfere with the endocrine system of aquatic organisms. The effect of these chemicals on biota and human populations is of high public concern but remains poorly understood, especially in aquatic environments of South America. The aim of this study was to investigate the bioavailability of POPs and the related effects in caged male tilapia (Oreochromis niloticus) in four cascading reservoirs of the Iguaçu River, Southern Brazil...
May 15, 2018: Environmental Pollution
https://www.readbyqxmd.com/read/29775890/triterpenic-acids-enriched-fraction-from-cyclocarya-paliurus-attenuates-non-alcoholic-fatty-liver-disease-via-improving-oxidative-stress-and-mitochondrial-dysfunction
#12
Meng-Ge Zhao, Xue-Ping Sheng, Ya-Ping Huang, Yi-Ting Wang, Cui-Hua Jiang, Jian Zhang, Zhi-Qi Yin
The effects of triterpenic acids-enriched fraction from Cyclocarya paliurus (CPT) on nonalcoholic fatty liver disease (NAFLD) were investigated using in vivo and in vitro models. In high fat diet-induced Wister rats, CPT significantly increased superoxide dismutase (SOD) activity and glutathione/oxidized glutathione (GSH/GSSG) ratio, reduced malondialdehyde (MDA) and protein carbonyl (PCO) levels. Moreover, CPT restored mitochondrial membrane potential dysfunction, decreased cytochrome P450 enzyme 2E1 (CYP2E1) activity, improved nuclear factor erythroid 2-related factor 2 (Nrf2) and Nrf2-mediated antioxidant enzyme heme oxygenase1 (HO-1) expression...
May 15, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29775551/pharmacogenetic-associations-with-cytochrome-p450-in-antiretroviral-therapy-what-does-the-future-hold
#13
Gabriel Stillemans, Leila Belkhir, Dennis A Hesselink, Vincent Haufroid, Laure Elens
Several antiretroviral drugs used to treat infection with the Human Immunodeficiency Virus (HIV) are substrates of enzymes belonging to the cytochrome P450 (CYP) superfamily, which are polymorphically expressed. It may therefore be useful to take into account the genetic variation in these enzymes to predict the likelihood of anti-HIV treatment success, toxicity and the potential for drug-drug interactions. Areas covered: In this manuscript, the authors discuss the current state of knowledge regarding pharmacogenetic associations between CYP and all major antiretrovirals, as well as the importance of these associations...
May 18, 2018: Expert Opinion on Drug Metabolism & Toxicology
https://www.readbyqxmd.com/read/29775322/prediction-of-human-cytochrome-p450-inhibition-using-a-multi-task-deep-autoencoder-neural-network
#14
Xiang Li, Youjun Xu, Luhua Lai, Jianfeng Pei
Adverse side effects of drug-drug interactions induced by human cytochrome P450 (CYP450) inhibition is an important consideration in drug discovery. It is highly desirable to develop computational models that can predict the inhibitive effect of a compound against a specific CYP450 isoform. In this study, we developed a multi-task model for concurrent inhibition prediction of five major CYP450 isoforms, namely 1A2, 2C9, 2C19, 2D6, and 3A4. The model was built by training multi-task autoencoder deep neural network (DNN) on a large dataset containing more than 13000 compounds, extracted from PubChem BioAssay Database...
May 18, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29773554/nitidine-chloride-is-a-mechanism-based-inactivator-of-cyp2d6
#15
Xu Mao, Zi Xia Hu, Qian Wang, Na Zhang, Shen Zhi Zhou, Ying Peng, Jiang Zheng
Nitidine chloride (NC) is a benzophenanthridine alkaloid isolated from the roots of Zanthoxylum nitidum (Roxb.) DC, a widely used traditional herbal medicine. NC has been reported to reveal multiple pharmacologic properties. The inhibitory effects of NC on human cytochrome P450 enzymes were investigated in the present study. We found that NC caused time- and concentration-dependent inhibition of CYP2D6, and more than 50% of CYP2D6 activity was suppressed after 15 min incubation with NC at 100 μM in the primary incubation mixtures, with KI of 4...
May 17, 2018: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/29772747/involvement-of-cyp4f2-in-the-metabolism-of-a-novel-monophosphate-ester-prodrug-of-gemcitabine-and-its-interaction-potential-in-vitro
#16
Yedong Wang, Yuan Li, Jia Lu, Huixin Qi, Isabel Cheng, Hongjian Zhang
Compound- 3 is an oral monophosphate prodrug of gemcitabine. Previous data showed that Compound- 3 was more potent than gemcitabine and it was orally active in a tumor xenograft model. In the present study, the metabolism of Compound- 3 was investigated in several well-known in vitro matrices. While relatively stable in human and rat plasma, Compound- 3 demonstrated noticeable metabolism in liver and intestinal microsomes in the presence of NADPH and human hepatocytes. Compound- 3 could also be hydrolyzed by alkaline phosphatase, leading to gemcitabine formation...
May 16, 2018: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/29772534/trapping-methods-for-probing-functional-intermediates-in-nitric-oxide-synthases-and-related-enzymes
#17
Tobias Michael Hedison, Sam Hay, Nigel Shaun Scrutton
The three mammalian isoforms of nitric oxide synthase (NOS) produce the signalling molecule nitric oxide (NO) from L-arginine, molecular oxygen, and NADPH. NOS-generated NO is essential for many key biochemical processes and aberrant NO production is linked to the pathophysiology of many diseases. Over the past 40 years, the mechanism and structure of NOS have been studied extensively and there are many quality reviews and perspectives documenting the current hypotheses in the field. In this review, as an alternative perspective, we will describe some novel techniques and methodologies that have been used to trap functionally relevant conformational and kinetic states in the catalytic cycles of NOS and some structurally related diflavin oxidoreductase...
June 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/29771914/regulation-of-vitamin-d-metabolizing-enzymes-in-murine-renal-and-extrarenal-tissues-by-dietary-phosphate-fgf23-and-1-25-oh-2d3
#18
Larissa Kägi, Carla Bettoni, Eva M Pastor-Arroyo, Udo Schnitzbauer, Nati Hernando, Carsten A Wagner
BACKGROUND: The 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) together with parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) regulates calcium (Ca2+) and phosphate (Pi) homeostasis, 1,25(OH)2D3 synthesis is mediated by hydroxylases of the cytochrome P450 (Cyp) family. Vitamin D is first modified in the liver by the 25-hydroxylases CYP2R1 and CYP27A1 and further activated in the kidney by the 1α-hydroxylase CYP27B1, while the renal 24-hydroxylase CYP24A1 catalyzes the first step of its inactivation...
2018: PloS One
https://www.readbyqxmd.com/read/29771294/the-maize-lilliputian1-lil1-gene-encoding-a-brassinosteroid-cytochrome-p450-c-6-oxidase-is-involved-in-plant-growth-and-drought-response
#19
Giulia Castorina, Martina Persico, Massimo Zilio, Stefano Sangiorgio, Laura Carabelli, Gabriella Consonni
Background and Aims: Brassinosteroids (BRs) are plant hormones involved in many developmental processes as well as in plant-environment interactions. Their role was investigated in this study through the analysis of lilliputian1-1 (lil1-1), a dwarf mutant impaired in BR biosynthesis in maize (Zea mays). Methods: We isolated lil1-1 through transposon tagging in maize. The action of lil1 was investigated through morphological and genetic analysis. Moreover, by comparing lil1-1 mutant and wild-type individuals grown under drought stress, the effect of BR reduction on the response to drought stress was examined...
May 16, 2018: Annals of Botany
https://www.readbyqxmd.com/read/29770981/a-dehydrogenase-dual-hydrogen-abstraction-mechanism-promotes-estrogen-biosynthesis-can-we-expand-the-functional-annotation-of-the-aromatase-enzyme
#20
Angelo Spinello, Matic Pavlin, Lorenzo Casalino, Alessandra Magistrato
Cytochromes P450 (CYP450) are involved in the metabolism of exogenous compounds and in the synthesis of signaling molecules. Among the latter, human aromatase (HA) promotes estrogen biosynthesis, being a key pharmacological target against breast cancers. After decades of debate, the interest in gaining a comprehensive picture of HA catalysis has been renewed by the recent discovery that Compound I (Cpd I) is the reactive species of the peculiar aromatization step. Here, we provide for the first time a complete atomic-level picture of all controversial steps of estrogen biosynthesis...
May 17, 2018: Chemistry: a European Journal
keyword
keyword
13830
1
2
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read
×

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"