keyword
MENU ▼
Read by QxMD icon Read
search

microsome

keyword
https://www.readbyqxmd.com/read/28747995/assessment-of-inhibitory-effects-on-major-human-cytochrome-p450-enzymes-by-spasmolytics-used-in-the-treatment-of-overactive-bladder-syndrome
#1
Dominik Dahlinger, Sevinc Aslan, Markus Pietsch, Sebastian Frechen, Uwe Fuhr
BACKGROUND: The objective of this study was to examine the inhibitory potential of darifenacin, fesoterodine, oxybutynin, propiverine, solifenacin, tolterodine and trospium chloride on the seven major human cytochrome P450 enzymes (CYP) by using a standardized and validated seven-in-one cytochrome P450 cocktail inhibition assay. METHODS: An in vitro cocktail of seven highly selective probe substrates was incubated with human liver microsomes and varying concentrations of the seven test compounds...
July 2017: Therapeutic Advances in Urology
https://www.readbyqxmd.com/read/28745337/understanding-the-metabolism-of-the-anticancer-drug-triapine-electrochemical-oxidation-microsomal-incubation-and-in-vivo-analysis-using-lc-hrms
#2
Karla Pelivan, Lisa Frensemeier, Uwe Karst, Gunda Koellensperger, Bjoern Bielec, Sonja Hager, Petra Heffeter, Bernhard K Keppler, Christian R Kowol
α-N-Heterocyclic thiosemicarbazones are among the most promising ribonucleotide reductase inhibitors identified so far. Triapine, the most prominent representative of this class of substances, has been investigated in multiple phase I and II clinical trials. With regard to clinical practice, Triapine showed activity against hematological diseases, but ineffectiveness against a variety of solid tumors. However, the reasons are still vague and the amount of ADME (absorption, distribution, metabolism and excretion) data for Triapine available in the literature is very limited...
July 26, 2017: Analyst
https://www.readbyqxmd.com/read/28743078/metabolite-identification-of-azd8055-in-sprague-dawley-rats-after-a-single-oral-administration-using-ultra-performance-liquid-chromatography-and-mass-spectrometry
#3
Md Mamunur Rashid, Hyun-A Oh, Hyunbeom Lee, Byung Hwa Jung
AZD8055 is an ATP-competitive specific dual mTOR inhibitor and exhibited potent antitumor activity on several types of solid tumors. However, the metabolism of AZD8055 in the body still remains unknown. In this study, metabolite identification of AZD8055 was performed using ultra high-performance liquid chromatography-ion trap mass spectrometry (UHPLC-IT-MS) through both in vitro and in vivo approaches using rat liver microsomes (RLMs) and rat plasma, urine and feces, respectively. A total of eight putative metabolites (five phase I and three phase II) were identified, and a tentative metabolic pathway was suggested for the first time...
July 8, 2017: Journal of Pharmaceutical and Biomedical Analysis
https://www.readbyqxmd.com/read/28739829/inherent-oxidative-stress-in-lewis-rat-is-associated-with-resistance-to-toxoplasmosis
#4
William H Witola, Chi Yong Kim, Xuejin Zhang
The course of Toxoplasma gondii infection in rats closely resembles that in humans. However, compared to the Brown Norway (BN) rat, the Lewis (LEW) rat is extremely resistant to T. gondii infection. Thus, we performed RNA sequencing analysis of the LEW versus BN rat, with or without T. gondii infection, in order to unravel molecular factors directing robust and rapid early T. gondii-killing mechanisms in the LEW rat. We found that, compared to the uninfected BN rat, the uninfected LEW rat has inherently higher transcript levels of cytochrome enzymes [Cyp2d3, Cyp2d5 and Cybrd1 that catalyze generation of reactive oxygen species (ROS)], with concomitant higher levels of ROS...
July 24, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28737905/metabolism-of-t-2-toxin-in-farm-animals-and-human-in-vitro-and-in-chickens-in-vivo-using-ultra-high-performance-liquid-chromatography-quadrupole-time-of-flight-hybrid-mass-spectrometry-along-with-online-hydrogen-deuterium-exchange-technique
#5
Shupeng Yang, Marthe De Boevre, Huiyan Zhang, Karl De Ruyck, Feifei Sun, Jinzhen Zhang, Yue Jin, Yanshen Li, Zhanhui Wang, Suxia Zhang, Jinhui Zhou, Yi Li, Sarah De Saeger
After incubated with animals' and human liver microsomes, metabolites of phase I and II were investigated. A comparison was performed by ultrahigh performance liquid chromatography-quadrupole/time-of-flight coupled to mass spectrometry (UHPLC-Q/TOF). Consequently, a total of four phase I metabolites and three glucuronide binding metabolites of T-2 toxin were discovered. Although a significant metabolic difference was observed among six species, HT-2 toxin was the major product in all species. In addition, the in vivo metabolism of T-2 toxin after oral administration was also investigated in chickens, In total, 18 metabolites were detected, of which 13 were novel, to our knowledge, and reported for the first time...
July 24, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28737724/time-dependent-inhibition-of-cyp2c8-and-cyp2c19-by-hedera-helix-extracts-a-traditional-respiratory-herbal-medicine
#6
Shaheed Ur Rehman, In Sook Kim, Min Sun Choi, Seung Hyun Kim, Yonghui Zhang, Hye Hyun Yoo
The extract of Hedera helix L. (Araliaceae), a well-known folk medicine, has been popularly used to treat respiratory problems, worldwide. It is very likely that this herbal extract is taken in combination with conventional drugs. The present study aimed to evaluate the effects of H. helix extract on cytochrome P450 (CYP) enzyme-mediated metabolism to predict the potential for herb-drug interactions. A cocktail probe assay was used to measure the inhibitory effect of CYP. H. helix extracts were incubated with pooled human liver microsomes or CYP isozymes with CYP-specific substrates, and the formation of specific metabolites was investigated to measure the inhibitory effects...
July 24, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28731962/polymorphisms-in-cytochrome-p450-oxidoreductase-and-its-effect-on-drug-metabolism-and-efficacy
#7
Liang Gong, Cong-Min Zhang, Jin-Feng Lv, Hong-Hao Zhou, Lan Fan
Cytochrome P450 oxidoreductase (POR) has played a potential role in the metabolism of drugs and steroids by supplying electrons to microsomal cytochrome P450 (CYP) enzymes. More than 200 different POR mutations and polymorphisms causing more than 130 amino acid changes in the POR protein have been reported since 2004. A503V is a common amino acid sequence variant encoded by POR*28, whereas A287P and R457H are the most common disease-causing mutations in Europeans and Asians, respectively. Polymorphisms in the POR gene can affect POR activity, CYP-mediated drug metabolism activities, and the efficacy of several clinically used drugs...
July 20, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28730856/in-vitro-drug-drug-interactions-of-budesonide-inhibition-and-induction-of-transporters-and-cytochrome-p450-enzymes
#8
Nancy Chen, Donghui Cui, Qing Wang, Zhiming Wen, Richard D Finkelman, Devin Welty
1. Budesonide is a glucocorticoid used in the treatment of several respiratory and gastrointestinal inflammatory diseases. Glucocorticoids have been demonstrated to induce cytochrome P450 (CYP) 3A and the efflux transporter P-glycoprotein (P-gp). This study aimed to evaluate the potential of budesonide to act as a perpetrator or a victim of transporter- or CYP-mediated drug-drug interactions (DDIs). 2. In vitro studies were conducted for P-gp, breast cancer resistance protein and organic anion and cation transporters (OATP1B1, OATP1B3, OAT1, OAT3, OCT2) in transporter-transfected cells...
July 21, 2017: Xenobiotica; the Fate of Foreign Compounds in Biological Systems
https://www.readbyqxmd.com/read/28728133/zebrafish-have-an-ethanol-inducible-hepatic-4-nitrophenol-hydroxylase-that-is-not-cyp2e1-like
#9
Jessica H Hartman, Jordan S Kozal, Richard T Di Giulio, Joel N Meyer
Zebrafish are an attractive model organism for toxicology; however, an important consideration in translating between species is xenobiotic metabolism/bioactivation. CYP2E1 metabolizes small hydrophobic molecules, e.g. ethanol, cigarette smoke, and diesel exhaust components. CYP2E1 is thought to only be conserved in mammals, but recent reports identified homologous zebrafish cytochrome P450s. Herein, ex vivo biochemical measurements show that unlike mammals, zebrafish possess a low-affinity 4-nitrophenol hydroxylase (Km ∼0...
July 10, 2017: Environmental Toxicology and Pharmacology
https://www.readbyqxmd.com/read/28726718/inhibitory-effects-of-trapping-agents-of-sulfur-drug-reactive-intermediates-against-major-human-cytochrome-p450-isoforms
#10
Jasleen K Sodhi, Erlie Marie Delarosa, Jason S Halladay, James P Driscoll, Teresa Mulder, Patrick M Dansette, S Cyrus Khojasteh
In some cases, the formation of reactive species from the metabolism of xenobiotics has been linked to toxicity and therefore it is imperative to detect potential bioactivation for candidate drugs during drug discovery. Reactive species can covalently bind to trapping agents in in vitro incubations of compound with human liver microsomes (HLM) fortified with β-nicotinamide adenine dinucleotide phosphate (NADPH), resulting in a stable conjugate of trapping agent and reactive species, thereby facilitating analytical detection and providing evidence of short-lived reactive metabolites...
July 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28725961/the-plasma-membrane-proteome-of-medicago-truncatula-roots-as-modified-by-arbuscular-mycorrhizal-symbiosis
#11
Achref Aloui, Ghislaine Recorbet, Christelle Lemaître-Guillier, Arnaud Mounier, Thierry Balliau, Michel Zivy, Daniel Wipf, Eliane Dumas-Gaudot
In arbuscular mycorrhizal (AM) roots, the plasma membrane (PM) of the host plant is involved in all developmental stages of the symbiotic interaction, from initial recognition to intracellular accommodation of intra-radical hyphae and arbuscules. Although the role of the PM as the agent for cellular morphogenesis and nutrient exchange is especially accentuated in endosymbiosis, very little is known regarding the PM protein composition of mycorrhizal roots. To obtain a global overview at the proteome level of the host PM proteins as modified by symbiosis, we performed a comparative protein profiling of PM fractions from Medicago truncatula roots either inoculated or not with the AM fungus Rhizophagus irregularis...
July 19, 2017: Mycorrhiza
https://www.readbyqxmd.com/read/28724258/lldt-288-a-novel-triptolide-analogue-exhibits-potent-antitumor-activity-in-vitro-and-in-vivo
#12
Hongtao Xu, Xiaoting Fan, Guanjun Zhang, Xiaoyu Liu, Zhihong Li, Yuanchao Li, Biao Jiang
(14S)-14β-(1-(2-morpholinoethyl)-1H-indazol-5-ylamino)mthylepitriptolide (LLDT-288) was a novel C14β-heterocycle aminomethyl substituent triptolide analogue, which showed comparable cytotoxicity to triptolide. Here we demonstrated that LLDT-288 displayed broad-spectrum, potent antitumor activity, effectively against drug-resistance cancer cells, and induced apoptosis in vitro, but exerted low toxicity. Moreover, it exhibited a remarkable microsomal stability, and showed no inhibitory effects on different cytochrome P450 isoforms...
July 15, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28723166/automated-3-d-printed-arrays-to-evaluate-genotoxic-chemistry-e-cigarettes-and-water-samples
#13
Karteek Kadimisetty, Spundana Malla, James F Rusling
A novel, automated, low cost, three-dimensional (3-D) printed microfluidic array was developed to detect DNA damage from metabolites of chemicals in environmental samples. The electrochemiluminescent (ECL) detection platform incorporates layer-by-layer (LbL) assembled films of microsomal enzymes, DNA and an ECL-emitting ruthenium metallopolymer in ∼10 nm deep microwells. Liquid samples are introduced into the array, metabolized by the human enzymes, products react with DNA if possible, and DNA damage is detected by ECL with a camera...
May 26, 2017: ACS Sensors
https://www.readbyqxmd.com/read/28720332/synthesis-and-biological-evaluation-of-fluoro-substituted-3-4-dihydroquinazoline-derivatives-for-cytotoxic-and-analgesic-effects
#14
Jin Han Kim, Hui Rak Jeong, Da Woon Jung, Hong Bin Yoon, Sun Young Kim, Hyoung Ja Kim, Kyung-Tae Lee, Vinicius M Gadotti, Junting Huang, Fang-Xiong Zhang, Gerald W Zamponi, Jae Yeol Lee
As a bioisosteric strategy to overcome the poor metabolic stability of lead compound KYS05090S, a series of new fluoro-substituted 3,4-dihydroquinazoline derivatives was prepared and evaluated for T-type calcium channel (Cav3.2) block, cytotoxic effects and liver microsomal stability. Among them, compound 8h (KCP10068F) containing 4-fluorobenzyl amide and 4-cyclohexylphenyl ring potently blocked Cav3.2 currents (>90% inhibition) at 10μM concentration and exhibited cytotoxic effect (IC50=5.9μM) in A549 non-small cell lung cancer cells that was comparable to KYS05090S...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28720324/synthesis-and-diabetic-neuropathic-pain-alleviating-effects-of-2n-pyrazol-3-yl-methylbenzo-d-isothiazole-1-1-dioxide-derivatives
#15
Jin Ri Hong, Young Jin Choi, Gyochang Keum, Ghilsoo Nam
A novel series of fused-benzensulfonamide 2-N-(pyrazol-3-yl)methylbenzo[d]isothiazole-1,1-dioxide derivatives was designed and synthesized as metabolically stable T-type calcium channel inhibitors. Several compounds, 9, 10, and 17, displayed potent T-type channel inhibitory activity. Among them, compounds 10 and 17 showed good metabolic stability in human liver microsomes, and low hERG channel and CYP450 inhibition. Compound 10 exhibited diabetic neuropathic pain-alleviating effects in a streptozotocin-induced peripheral diabetic neuropathy (PDN) model...
July 8, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28717107/human-plasma-and-urinary-metabolic-profiles-of-trimethylamine-and-trimethylamine-n-oxide-extrapolated-using-a-simple-physiologically-based-pharmacokinetic-model
#16
Makiko Shimizu, Hiroshi Yamazaki
Trimethylamine, a dietary- and medicinal carnitine-derived amine, is extensively metabolized by liver to non-malodorous trimethylamine N-oxide. Although trimethylamine and trimethylamine N-oxide under daily dietary consumption or carnitine treatment are generally regarded as nontoxic, they have been, and remain, of toxicological and clinical interest because of their potential association with atherosclerosis. The aim of the current study was to model the pharmacokinetics of trimethylamine after oral administration of trimethylamine in humans and compare the results with reported measured values...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28716728/cytochrome-p450-3a-selectively-affects-the-pharmacokinetic-interaction-between-erlotinib-and-docetaxel-in-rats
#17
Xuan Qin, Jian Lu, Peili Wang, Peipei Xu, Mingyao Liu, Xin Wang
Erlotinib as a first-line drug is used in non-small cell lung cancer (NSCLC) patients with sensitive EGFR mutations, while resistance to this drug will occur after several years of treatment. Therefore, the microtubule disturber docetaxel is introduced as combined regimen in clinical trials. This report investigated the potentials and mechanisms of drug-drug interaction (DDI) between erlotinib and docetaxel using wild type (WT) and Cyp3a1/2 knockout (KO) rats. The erlotinib O-demethylation and docetaxel hydroxylation reactions in the absence or the presence of another drug were analyzed in vitro via the assay of rat liver microsomes...
July 14, 2017: Biochemical Pharmacology
https://www.readbyqxmd.com/read/28713081/gene-polymorphism-of-xenobiotic-detoxification-in-children-with-bronchial-asthma
#18
Liudmila Y Lytvynets
INTRODUCTION: Children are the most susceptible to harmful external factors due to the incomplete development of all functional body systems. The ecological situation the problem of influence of genetic and environmental factors on the pathogenesis of chronic respiratory diseases in children and its investigation is very impotent today. Among it the bronchial asthma is a leader among bronchial and pulmonary diseases caused by the influence of pneumotropic pollutants. The aim of our research was to study the phenotypic characteristics of asthma in Pre-Carpathian children with different types of allelic gene polymorphism of the first phase of xenobiotic detoxification of microsomal epoxide hydrolases (mEPHX1)...
2017: Wiadomości Lekarskie: Organ Polskiego Towarzystwa Lekarskiego
https://www.readbyqxmd.com/read/28711713/surprisingly-high-stability-of-the-a%C3%AE-oligomer-eliminating-all-d-enantiomeric-peptide-d3-in-media-simulating-the-route-of-orally-administered-drugs
#19
Anne Elfgen, Beatrix Santiago-Schübel, Lothar Gremer, Janine Kutzsche, Dieter Willbold
The aggregation of the amyloid β protein (Aβ) plays an important role in the pathology of Alzheimer's disease. Previously, we have developed the all-d-enantiomeric peptide D3, which is able to eliminate neurotoxic Aβ oligomers in vitro and improve cognition in a transgenic Alzheimer's disease mouse model in vivo even after oral administration. d-Peptides are expected to be more resistant against enzymatic proteolysis compared to their l-enantiomeric equivalents, and indeed, a pharmacokinetic study with tritiated D3 revealed the oral bioavailability to be about 58%...
July 12, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28711625/suppressing-mpges-1-expression-by-sinomenine-ameliorates-inflammation-and-arthritis
#20
Hua Zhou, Jian-Xin Liu, Jin-Fang Luo, Chun-Song Cheng, Elaine Lai-Han Leung, Ying Li, Xiao-Hui Su, Zhong-Qiu Liu, Ting-Bo Chen, Fu-Gang Duan, Yan Dong, Yi-Han Zuo, Chong Li, Chon Kit Lio, Ting Li, Pei Luo, Ying Xie, Xiao-Jun Yao, Pei-Xun Wang, Liang Liu
Recently, microsomal prostaglandin E synthase 1 (mPGES-1) has attracted much attention from pharmacologists as a promising strategy and an attractive target for treating various types of diseases including rheumatoid arthritis (RA), which could preserve the anti-inflammatory effect while reducing the adverse effects often occur during administration of Non-steroidal anti-inflammatory drugs (NSAIDs). Here, we report that Sinomenine (SIN) decreased prostaglandin (PG)E2 levels without affecting prostacyclin (PG)I2 and thromboxane (TX)A2 synthesis via selective inhibiting mPGES-1 expression, a possible reason of low risk of cardiovascular event compared with NSAIDs...
July 12, 2017: Biochemical Pharmacology
keyword
keyword
116965
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"