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https://www.readbyqxmd.com/read/28545313/effects-of-rosmarinic-acid-on-acetaminophen-induced-hepatotoxicity-in-male-wistar-rats
#1
Parisa Hasanein, Maryam Sharifi
CONTEXT: Drug-induced liver injury is a significant worldwide clinical problem. Rosmarinic acid (RA), a natural phenol, has antioxidant effects. OBJECTIVE: The effects of RA against acetaminophen (N-acetyl-p-amino-phenol (APAP))-induced oxidative damage and hepatotoxicity in rats were investigated. MATERIALS AND METHODS: Male Wistar rats were pretreated with RA (10, 50 and 100 mg/kg, i.g.) for one week. On day 7, rats received APAP (500 mg/kg, i...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28545186/gallium-nanoparticle-mediated-reduction-of-brain-specific-serine-protease-4-in-an-experimental-metastatic-cancer-model
#2
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/28542812/modulating-nasal-mucosal-permeation-using-metabolic-saturation-and-enzyme-inhibition-techniques
#3
Varsha Dhamankar, Maureen D Donovan
OBJECTIVE: Presystemic elimination resulting from local enzymatic degradation can play a key role in limiting the bioavailability of intranasally administered drugs. The aim of this study was to evaluate the transfer of a metabolically susceptible drug across the nasal mucosa to illustrate the relative contributions of drug diffusivity and metabolic susceptibility on overall nasal mucosal permeation and to understand the effects of changes in enzymatic activity on the transfer across nasal epithelial and submucosal tissues...
May 23, 2017: Journal of Pharmacy and Pharmacology
https://www.readbyqxmd.com/read/28528513/the-expansive-role-of-oxylipins-on-platelet-biology
#4
REVIEW
Jennifer Yeung, Megan Hawley, Michael Holinstat
In mammals, three major oxygenases, cyclooxygenases (COXs), lipoxygenases (LOXs), and cytochrome P450 (CYP450), generate an assortment of unique lipid mediators (oxylipins) from polyunsaturated fatty acids (PUFAs) which exhibit pro- or anti-thrombotic activity. Over the years, novel oxylipins generated from the interplay of theoxygenase activity in various cells, such as the specialized pro-resolving mediators (SPMs), have been identified and investigated in inflammatory disease models. Although platelets have been implicated in inflammation, the role and mechanism of these SPMs produced from immune cells on platelet function are still unclear...
May 20, 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28524079/assembly-of-hepatocyte-spheroids-using-magnetic-3d-cell-culture-for-cyp450-inhibition-induction
#5
Pujan K Desai, Hubert Tseng, Glauco R Souza
There is a significant need for in vitro methods to study drug-induced liver injury that are rapid, reproducible, and scalable for existing high-throughput systems. However, traditional monolayer and suspension cultures of hepatocytes are difficult to handle and risk the loss of phenotype. Generally, three-dimensional (3D) cell culture platforms help recapitulate native liver tissue phenotype, but suffer from technical limitations for high-throughput screening, including scalability, speed, and handling. Here, we developed a novel assay for cytochrome P450 (CYP450) induction/inhibition using magnetic 3D cell culture that overcomes the limitations of other platforms by aggregating magnetized cells with magnetic forces...
May 18, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28506184/complications-of-psychotropic-and-pain-medications-in-an-ultrarapid-metabolizer-patient-at-the-upper-1-of-cytochrome-p450-cyp450-function-quantified-by-combinatorial-cyp450-genotyping
#6
Gualberto Ruaño, Karen Larsen, Mohan Kocherla, James Samuel Graydon, Jonathan Kost
A 44-year-old Caucasian woman presented with a history of empirical treatment with 20 pain and psychotropic medications, as well as dual comorbidity of intractable pain and depression. A multiple gain-of-function profile in the CYP450 family of cytochrome P450 (CYP450) drug metabolism isoenzymes was discovered. The patient was a homozygote of suprafunctional alleles for both CYP2D6 ((*)35/(*)35) and CYP2C19 ((*)17/(*)17) genes and functional alleles for CYP2C9 ((*)1/(*)1), which account for aggregate drug metabolism function at the upper 1% of the population...
May 16, 2017: Journal of Pain & Palliative Care Pharmacotherapy
https://www.readbyqxmd.com/read/28494548/-the-role-of-cytochrome-p450-in-nonalcoholic-fatty-liver-induced-by-high-fat-diet-a-gene-expression-profile-analysis
#7
Y Liu, F Cheng, Y X Luo, P Hu, H Ren, M L Peng
Objective: To clarify the role of cytochrome P450 in nonalcoholic fatty liver disease (NAFLD) by RNA-Seq and bioinformatics analysis. Methods: A total of 20 male C57BL/6 mice were used. Ten mice were fed with high-fat diet (D12492, 60% kcal fat) for 16 weeks to establish a mouse model of NAFLD, and the other 10 mice were fed with low-fat diet (D12450B, 10% kcal fat) as control group. At the end of the experiment, the body weight, liver weight, and hepatic triglyceride (TG) content were measured. Meanwhile, HE staining and RNA-Seq analysis were performed for the liver tissues...
April 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28486989/postnatal-treatment-using-curcumin-supplements-to-amend-the-damage-in-vpa-induced-rodent-models-of-autism
#8
Maha Al-Askar, Ramesa Shafi Bhat, Manar Selim, Laila Al-Ayadhi, Afaf El-Ansary
BACKGROUND: Valproic acid (VPA) is used as a first-line antiepileptic agent and is undergoing clinical trials for use as a treatment for many disorders. Mothers undergoing VPA treatment during early pregnancy reportedly show increased rates of autism among their offspring. The benefits of curcumin supplementation were investigated using an animal model of VPA-induced autism. METHODS: The study was performed using a rodent model of autism by exposing rat fetuses to valproic acid (VPA) on the 12...
May 10, 2017: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/28473993/salvia-miltiorrhiza-roots-against-cardiovascular-disease-consideration-of-herb-drug-interactions
#9
REVIEW
Feng Chen, Li Li, Dan-Dan Tian
Salvia miltiorrhiza root (Danshen) is widely used in Asia for its cardiovascular benefits and contains both hydrophilic phenolic acids and lipophilic tanshinones, which are believed to be responsible for its therapeutic efficacy. This review summarized the effects of these bioactive components from S. miltiorrhiza roots on pharmacokinetics of comedicated drugs with mechanic insights regarding alterations of protein binding, enzyme activity, and transporter activity based on the published data stemming from both in vitro and in vivo human studies...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28470107/cyp450-genotype-and-aggressive-behavior-on-selective-serotonin-reuptake-inhibitors
#10
Corine Ekhart, Maja Matic, Agnes Kant, Eugène van Puijenbroek, Ron van Schaik
AIM: Genetic variants for selective serotonin reuptake inhibitor (SSRI) metabolizing enzymes have been hypothesized to be a risk factor for aggression as adverse drug effect of SSRIs. Our aim was to assess the possible involvement of these polymorphisms on aggression when using SSRIs. MATERIALS & METHODS: A retrospective noninterventional case-control study was performed on 18 cases. The genetic profile of two main genes involved in the metabolism of SSRIs was determined, and predicted phenotype frequencies were compared with Dutch controls and literature data...
May 4, 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28461741/functional-characterization-of-wild-type-and-24-cyp2d6-allelic-variants-on-gefitinib-metabolism-in-vitro
#11
Ping Fang, Xiang Zheng, Jiayang He, Honglei Ge, Pengfei Tang, Jianping Cai, Guoxin Hu
BACKGROUND: Cytochrome P450 2D6 (CYP2D6), a member of the CYP450 enzyme super family, is a polymorphic enzyme that metabolizes ~25% of therapeutic drugs. CYP2D6 exhibits significant genetic polymorphisms which might cause adverse effects and therapeutic failures of some drugs. OBJECTIVE: The purpose of this study was to evaluate the catalytic activities of 22 novel CYP2D6 alleles (CYP2D6*87, *88, *89, *90, *91, *92, *93, *94, *95, *96, *97, *98, R25Q, F164L, E215K, F219S, V327M, D336N, V342M, R344Q, R440C, R497C) on the metabolism of gefitinib in vitro...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28446877/exploring-the-role-of-cyp3a4-mediated-drug-metabolism-in-the-pharmacological-modulation-of-nitric-oxide-production
#12
José Pérez-Del Palacio, Caridad Díaz, Noemí Vergara, Francesca Algieri, Alba Rodríguez-Nogales, Nuria de Pedro, M Elena Rodríguez-Cabezas, Olga Genilloud, Julio Gálvez, Francisca Vicente
Nitric-oxide synthase, the enzyme responsible for mammalian nitric oxide generation, and cytochrome P450, the major enzymes involved in drug metabolism, share striking similarities. Therefore, it makes sense that cytochrome P450 drug mediated biotransformations might play an important role in the pharmacological modulation of nitric oxide synthase. In this work, we have undertaken an integrated in vitro assessment of the hepatic metabolism and nitric oxide modulation of previously described dual inhibitors (imidazoles and macrolides) of these enzymes in order assess the implication of CYP450 activities over production of nitric oxide...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28442442/prostaglandins-and-other-lipid-mediators-polm-special-issue-of-the-6th-european-workshop-on-lipid-mediators-role-of-m%C3%A3-ller-cell-cytochrome-p450-2c44-in-murine-retinal-angiogenesis
#13
Jiong Hu, Alexandra Geyer, Sarah Dziumbla, Khader Awwad, Darryl C Zeldin, Wolf-Hagen Schunck, Rüdiger Popp, Timo Frömel, Ingrid Fleming
Polyunsaturated fatty acids (PUFA) and their cytochrome P450 (CYP450) metabolites have been linked to angiogenesis and vessel homeostasis. However, the role of individual CYP isoforms and their endogenous metabolites in those processes are not clear. Here, we focused on the role of Cyp2c44 in postnatal retinal angiogenesis and report that Cyp2c44 is highly expressed in Müller glial cells in the retina. The constitutive as well as inducible postnatal genetic deletion of Cyp2c44 resulted in an increased vessel network density without affecting vessel radial expansion during the first postnatal week...
April 22, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28433551/in-vitro-investigation-of-metabolic-profiling-of-newly-developed-topoisomerase-inhibitors-ethyl-fluorescein-hydrazones-etflhs-in-rlms-by-lc-ms-ms
#14
Adnan A Kadi, Nasser S Al-Shakliah, Wencui Yin, A F M Motiur Rahman
Metabolic profiling of newly reported five topoisomerase inhibitors namely ethyl fluorescein hydrazones (EtFLHs) were studied in rat liver microsomes (RLMs) and the data were acquired in a liquid chromatography (LC) ion trap mass spectrometry. Hydroxyl group containing EtFLHs derivatives (1-3) were bio-transformed into hydrolyzed, mono-hydroxylated and hydrolyzed together with mono-hydroxylated metabolites. On the other hand, nitro and methoxy groups containing EtFLHs derivatives (4-5) were bio-transformed into hydrolyzed, hydrolyzed together with mono-hydroxylated and azo-reductive metabolites in the presence of NADPH...
April 6, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
https://www.readbyqxmd.com/read/28431455/uhplc-q-tof-ms-ms-based-screening-and-characterization-of-metabolites-of-cnidilin-in-human-liver-microsomes
#15
Lin Yuan, Yuqian Zhang, Man Liao, Yanyan Liu, Changchen Wan, Lantong Zhang
Cnidilin is an active natural furocoumarin ingredient originating from well-known traditional Chinese medicine Radix Angelicae Dahuricae. In the present study, an efficient approach was developed for the screening and identification of cnidilin metabolites using ultra-high-performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry. In this approach, an on-line data acquisition method multiple mass defect filter combined with dynamic background subtraction was developed to trace all probable metabolites...
April 21, 2017: Biomedical Chromatography: BMC
https://www.readbyqxmd.com/read/28428023/cyp450s-analysis-across-spiny-lobster-metamorphosis-identifies-a-long-sought-missing-link-in-crustacean-development
#16
Tomer Ventura, Utpal Bose, Quinn P Fitzgibbon, Gregory G Smith, P Nicholas Shaw, Scott F Cummins, Abigail Elizur
Cytochrome P450s (CYP450s) are a rapidly evolving family of enzymes, making it difficult to identify bona fide orthologs with notable lineage-specific exceptions. In ecdysozoans, a small number of the most conserved orthologs include enzymes which metabolize ecdysteroids. Ecdysone pathway components were recently shown in a decapod crustacean but with a notable absence of shade, which is important for converting ecdysone to its active form, 20-hydroxyecdysone (20HE), suggesting that another CYP450 performs a similar function in crustaceans...
April 17, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28423275/single-or-multiple-access-channels-to-the-cyp450s-active-site-an-answer-from-free-energy-simulations-of-the-human-aromatase-enzyme
#17
Alessandra Magistrato, Jacopo Sgrignani, Rolf Krause, Andrea Cavalli
Cytochromes P450 (CYP450s), in particular, CYP19A1 and CYP17A1, are key clinical targets of breast and prostate anticancer therapies, critical players in drug metabolism, and their overexpression in tumors is associated with drug resistance. In these enzymes, ligand (substrates, drugs) metabolism occurs in deeply buried active sites accessible only via several grueling channels, whose exact biological role remains unclear. Gaining direct insights on the mechanism by which ligands travel in and out is becoming increasingly important given that channels are involved in the modulation of binding/dissociation kinetics and the specificity of ligands toward a CYP450...
May 4, 2017: Journal of Physical Chemistry Letters
https://www.readbyqxmd.com/read/28421287/-age-89-years-depression-fall-with-pelvic-fracture-severe-confusion-serotonin-syndrome-differential-diagnosis-importance-of-cyp450-and-economic-considerations
#18
REVIEW
W Weinrebe, A Moutaouakil, K Risz, M Martin, K Jeckelmann, S Goetz
A case study of an 89-year-old patient is reported, who was admitted to hospital because of immobility due to pain. After the cause of the pain could initially be clarified and treated, the further clinical course in this very old woman showed an alarming symptom complex of agitation, confusion and cognitive deterioration, which took on grave forms. The work-up of this case showed a typical constellation of pain and depression in old age; however, the pharmaceutical treatment in this case is not atypical and could lead to a severe serotonin syndrome...
April 18, 2017: Zeitschrift Für Gerontologie und Geriatrie
https://www.readbyqxmd.com/read/28421119/influences-of-realgar-indigo-naturalis-a-traditional-chinese-medicine-formula-on-the-main-cyp450-activities-in-rats-using-a-cocktail-method
#19
Huan-Hua Xu, Fei-Ran Hao, Mei-Xi Wang, Si-Jia Ren, Ming Li, Hong-Ling Tan, Yu-Guang Wang, Xiang-Lin Tang, Cheng-Rong Xiao, Qian-De Liang, Yue Gao, Zeng-Chun Ma
The purpose of this work was to study the influences of Realgar-Indigo naturalis (RIF) and its principal element realgar on 4 main cytochrome P450 enzymes activities in rats. A simple and efficient cocktail method was developed to detect the four probe drugs simultaneously. In this study, Wistar rats were administered intragastric RIF and realgar for 14 days; mixed probe drugs were injected into rats by caudal vein. Through analyzing the pharmacokinetic parameter of mixed probe drugs in rats, we can calculate the CYPs activities...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28415021/in-vitro-investigation-of-metabolic-profiling-of-a-potent-topoisomerase-inhibitors-fluorescein-hydrazones-flhs-in-rlms-by-lc-ms-ms
#20
A F M Motiur Rahman, Nasser S Al-Shakliah, Wencui Yin, Adnan A Kadi
Metabolic profiling of newly reported two topoisomerase inhibitors namely fluorescein hydrazones (FLHs) were studied in rat liver microsomes (RLMs) and the data were acquired in a liquid chromatography (LC) ion trap mass spectrometry. (E)-3',6'-dihydroxy-2-((2-nitrobenzylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (1) was bio-transformed into two mono-hydroxylated, one double hydroxylated and a tetra hydroxylated metabolites, on the other hand, (Z)-3',6'-dihydroxy-2-((2-oxoindolin-3-ylidene)amino)spiro[isoindoline-1,9'-xanthen]-3-one (2) was bio-transformed into eight possible metabolites by cleavage reduction, hydroxylation, cleavage reduction together with hydroxylated and azo-reduction in RLMs in presence of NADPH-generating system...
April 10, 2017: Journal of Chromatography. B, Analytical Technologies in the Biomedical and Life Sciences
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