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Cytochrome 450

Fadzilah Adibah Abd Majid, Nur Syukriah Ab Rahman, Effendy Abd Wahid, Ain Nabihah Zainudin, Siti Nurazwa Zainol, Hassan Fahmi Ismail, Tet Soon Wong, K Vijaya Bhargava, Nirbhay Kumar Tiwari, Sanjeev Giri
Drug interaction of SynacinnTM polyherbal with known diabetic drugs is unknown. SynacinnTM contains standardized extracts of five herbal against gallic acid, curcumin, rosmarinic acid, catechin and andrographolide. SynacinnTM and its five standard markers were analysed for its possible interaction with CYP450 enzymes assay. This study was conducted using liquid chromatography-tandem mass spectroscopy (LC-MS/MS) using probe substrates using human liver microsomes against CYP1A2, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP3A4(Midazolam) and CYP3A4 (Testosteron)...
March 13, 2018: Drug Metabolism Letters
Amelia Nathania Dong, Yan Pan, Uma Devi Palanisamy, Beow Chin Yiap, Nafees Ahemad, Chin Eng Ong
Genetic polymorphism of the cytochrome P450 (CYP) genes particularly affects CYP2D6 and CYP2C19 to a functionally relevant extent, and it is therefore crucial to elucidate the enzyme kinetic and molecular basis for altered catalytic activity of these allelic variants. This study explored the expression and function of the reported alleles CYP2D6*2, CYP2D6*10, CYP2D6*17, CYP2C19*23, CYP2C19*24, and CYP2C19*25 with respect to gene polymorphisms. Site-directed mutagenesis (SDM) was carried out to generate these six alleles...
March 10, 2018: Applied Biochemistry and Biotechnology
M Ghadimi, S Dashti-Khavidaki, M Shahali, M Gohari, M-R Khatami, A Alamdari
WHAT IS KNOWN AND OBJECTIVE: Oestrogens could inhibit the metabolism of drugs, such as calcineurin inhibitors, that are substrates for cytochrome P-450 microsomal enzymes. This study assessed the potential tacrolimus interaction with oral conjugated oestrogen in kidney transplant recipients who received conjugated oestrogen as prophylaxis against bleeding, before kidney biopsy. METHODS: In this case-control study, 13 kidney transplant recipients who received oral conjugated oestrogen as prophylaxis against uraemic bleeding before allograft biopsy were considered as cases...
February 28, 2018: Journal of Clinical Pharmacy and Therapeutics
Angela L Chiew, Christian Gluud, Jesper Brok, Nick A Buckley
BACKGROUND: Paracetamol (acetaminophen) is the most widely used non-prescription analgesic in the world. Paracetamol is commonly taken in overdose either deliberately or unintentionally. In high-income countries, paracetamol toxicity is a common cause of acute liver injury. There are various interventions to treat paracetamol poisoning, depending on the clinical status of the person. These interventions include inhibiting the absorption of paracetamol from the gastrointestinal tract (decontamination), removal of paracetamol from the vascular system, and antidotes to prevent the formation of, or to detoxify, metabolites...
February 23, 2018: Cochrane Database of Systematic Reviews
Eugene P Sokolov, Inna M Sokolova
Salinity is an important environmental factor affecting physiology of marine organisms. Osmoconformers such as marine mollusks maintain metabolic function despite changes of the osmolarity and composition of the cytosol during salinity shifts. Currently, metabolic responses to the salinity-induced changes of the intracellular milieu are not well understood. We studied the effects of osmolarity (450 vs. 900 mOsm) and compatible osmolytes (70-590 mM of taurine or betaine) on isolated gill mitochondria of a marine osmoconformer, the Pacific oyster Crassostrea gigas...
February 16, 2018: Mitochondrion
Sandeep Kumar Vishwakarma, Avinash Bardia, Chandrakala Lakkireddy, Raju Nagarapu, Md Aejaz Habeeb, Aleem Ahmed Khan
AIM: To develop appropriate humanized three-dimensional ex-vivo model system for drug testing. METHODS: Bioengineered humanized livers were developed in this study using human hepatic stem cells repopulation within the acellularized liver scaffolds which mimics with the natural organ anatomy and physiology. Six cytochrome P-450 probes were used to enable efficient identification of drug metabolism in bioengineered humanized livers. The drug metabolism study in bioengineered livers was evaluated to identify the absorption, distribution, metabolism, excretion and toxicity responses...
January 27, 2018: World Journal of Hepatology
Ana Carolina Rios Silvino, Gabriel Luiz Costa, Flávia Carolina Faustino de Araújo, David Benjamin Ascher, Douglas Eduardo Valente Pires, Cor Jesus Fernandes Fontes, Luzia Helena Carvalho, Cristiana Ferreira Alves de Brito, Tais Nobrega Sousa
[This corrects the article DOI: 10.1371/journal.pone.0160172.].
2018: PloS One
Brenton R Ware, Mitchell J Durham, Chase P Monckton, Salman R Khetani
Background and Aims: Modeling interactions between primary human hepatocytes (PHHs) and primary human liver sinusoidal endothelial cells (LSECs) in vitro can help elucidate human-specific mechanisms underlying liver physiology/disease and drug responses; however, existing hepatocyte/endothelial coculture models are suboptimal because of their use of rodent cells, cancerous cell lines, and/or nonliver endothelial cells. Hence, we sought to develop a platform that could maintain the long-term phenotype of PHHs and primary human LSECs...
March 2018: Cellular and Molecular Gastroenterology and Hepatology
Yinghao Wang, Shuisheng Wu, Chen Liu, Xuehua Lu, Zhihuang Chen
Herba Gelsemii elegantis (GE) has been frequently used as a Chinese folk medicine but has high acute toxicity. In Traditional Chinese Medicine, it may be detoxified by Ramulus et Folium Mussaendae pubescentis (MP), but the detoxification mechanism has remained elusive. The present study aimed to evaluate the detoxification mechanisms by which MP modulates the effect of GE in rats, including the inhibition of hepatic cytochrome P (CYP)450 and glutathione S-transferase (GST) enzymes. Male Sprague Dawley rats were orally administered GE at three doses (0...
January 2018: Experimental and Therapeutic Medicine
Michael M Yeboah, Md Abdul Hye Khan, Marla A Chesnik, Melissa Skibba, Lauren L Kolb, John D Imig
Background: Hepatorenal syndrome (HRS) is a life-threatening complication of advanced liver cirrhosis that is characterized by hemodynamic alterations in the kidney and other vascular beds. Cytochrome P(CYP)-450 enzymes metabolize arachidonic acid to epoxyeicosatrienoic acids (EETs) and 20-hydroxyeicosatetraenoic acids. These eicosanoids regulate blood pressure, vascular tone and renal tubular sodium transport under both physiological and pathophysiological states. Methods: Experiments were performed to investigate the role of the CYP system in the pathogenesis of renal dysfunction during cirrhosis...
January 19, 2018: Nephrology, Dialysis, Transplantation
J Kevin Baird, Katherine E Battle, Rosalind E Howes
The hypnozoite reservoir of Plasmodium vivax represents both the greatest obstacle and opportunity for ultimately eradicating this species. It is silent and cannot be diagnosed until it awakens and provokes a clinical attack with attendant morbidity, risk of mortality, and opportunities for onward transmission. The only licensed drug that kills hypnozoites is primaquine, which attacks the hypnozoite reservoir but imposes serious obstacles in doing so-at hypnozoitocidal doses, it invariably causes a threatening acute haemolytic anaemia in patients having an inborn deficiency in glucose-6-phosphate dehydrogenase (G6PD), affecting about 8% of people living in malaria endemic nations...
January 22, 2018: Malaria Journal
Zhaohui Liang, Jun Liu, Jimmy Xiangji Huang, Xing Zeng
OBJECTIVE: The genetic polymorphism of Cytochrome P450 (CYP 450) is considered as one of the main causes for adverse drug reactions (ADRs). In order to explore the latent correlations between ADRs and potentially corresponding single-nucleotide polymorphism (SNPs) in CYP450, three algorithms based on information theory are used as the main method to predict the possible relation. METHODS: The study uses a retrospective case-control study to explore the potential relation of ADRs to specific genomic locations and single-nucleotide polymorphism (SNP)...
January 14, 2018: Combinatorial Chemistry & High Throughput Screening
Mahshid Dehbozorgi, Behnam Kamalidehghan, Iman Hosseini, Zahra Dehghanfard, Mohammad Hossein Sangtarash, Maryam Firoozi, Fatemeh Ahmadipour, Goh Yong Meng, Massoud Houshmand
Polymorphisms in the cytochrome P (CYP) 450 family may cause adverse drug responses in individuals. Cytochrome P450 2C19 (CYP2C19) is a member of the CYP family, where the presence of the 681 G>A, 636 G>A and 806 C>T polymorphisms result in the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles, respectively. In the current study, the frequency of the CYP2C19*2, CYP2C19*3 and CYP2C19*17 alleles in an Iranian population cohort of different ethnicities were examined and then compared with previously published frequencies within other populations...
January 5, 2018: Molecular Medicine Reports
Guido J H Bastiaens, Alfred B Tiono, Joseph Okebe, Helmi E Pett, Sam A Coulibaly, Bronner P Gonçalves, Muna Affara, Alphonse Ouédraogo, Edith C Bougouma, Guillaume S Sanou, Issa Nébié, John Bradley, Kjerstin H W Lanke, Mikko Niemi, Sodiomon B Sirima, Umberto d'Alessandro, Teun Bousema, Chris Drakeley
BACKGROUND: Primaquine (PQ) actively clears mature Plasmodium falciparum gametocytes but in glucose-6-phosphate dehydrogenase deficient (G6PDd) individuals can cause hemolysis. We assessed the safety of low-dose PQ in combination with artemether-lumefantrine (AL) or dihydroartemisinin-piperaquine (DP) in G6PDd African males with asymptomatic P. falciparum malaria. METHODS AND FINDINGS: In Burkina Faso, G6PDd adult males were randomized to treatment with AL alone (n = 10) or with PQ at 0...
2018: PloS One
Ishfaq A Bukhari, Abdulrahman A Almotrefi, Osama Y Mohamed, Abeer A Al-Masri, Saeed Ahmed Sheikh
Fenofibrate is a peroxisome proliferator-activated receptor (PPAR)-α activator that lowers triglycerides and influences cytochrome P-450 (CYP-450) epoxygenase dependent arachidonic acid (AA) metabolism. CYP-450 epoxygenase metabolizes AA to epoxyeicosatrienoic acids (EETs). EETs have coronary dilating, cardiac and renal protective properties. Fibrates possess similar properties due to their CYP-450 epoxygenase inducing properties that leads to increase in endogenous EETs production. In the current investigations fenofibrate (100 mg/kg, orally) for two weeks decreased ischemia/reperfusion (I/R)-induced premature ventricular contractions (PVCs), ventricular tachycardia (VT) and ventricular fibrillation (VF) in the isolated rat hearts...
December 31, 2017: Fundamental & Clinical Pharmacology
Marta H Kubala, Yves A DeClerck
siRNA and shRNA-mediated knock down (KD) methods of regulating gene expression are invaluable tools for understanding gene and protein function. However, in the case that the KD of the protein of interest has a lethal effect on cells or the anticipated effect of the KD is time-dependent, unconditional KD methods are not appropriate. Conditional systems are more suitable in these cases and have been the subject of much interest. These include Ecdysone-inducible overexpression systems, Cytochrome P-450 induction system1, and the tetracycline regulated gene expression systems...
November 23, 2017: Journal of Visualized Experiments: JoVE
Florentino Lupercio, Jorge Romero, Bradley Peltzer, Carola Maraboto, David Briceno, Pedro Villablanca, Kevin Ferrick, Jay N Gross, Soo Kim, John Fisher, Luigi Di Biase, Andrew Krumerman
BACKGROUND: Direct oral anticoagulants (DOACs) and amiodarone are widely used in the treatment of non-valvular atrial fibrillation. The DOACs are P-glycoprotein (P-gp) and cytochrome p-450 (CYP3A4) substrates. DOAC levels may be increased by the concomitant use of potent dual P-gp/CYP3A4 inhibitors such as amiodarone, which can potentially translate into adverse clinical outcomes. We aimed to assess the efficacy and safety of drug-drug interaction by the concomitant use of DOACs and amiodarone...
December 21, 2017: American Journal of Medicine
Marie Febvre-James, Arnaud Bruyere, Marc Le Vee, Olivier Fardel
The inflammatory cytokine interleukin (IL)-6, which basically activates the JAK/STAT signaling pathway, is well-known to repress expression of hepatic cytochromes P-450 (CYPs) and transporters. Therapeutic proteins, like mAbs targeting IL-6 or its receptor, have been consequently demonstrated to restore full hepatic detoxification capacity, which results in inflammatory disease-related drug-drug interactions (idDDIs). In the present study, we investigated whether ruxolitinib, a small drug acting as a JAK1/2 inhibitor and currently used in the treatment of myeloproliferative neoplasms, may also counteract IL-6 repressing effects towards hepatic detoxifying systems...
November 21, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
Akbar Esmaeili, Meisam Khodaei
Rifampin (RIF) is a bactericidal antibiotic drug and potent inducer of hepatic and intestinal cytochrome P-450 (CYP-450) enzyme systems. Given by mouth or intravenously, it can cause numerous clinical drug interactions; thus, alternative systems of drug delivery that bypass some or all of its toxic effects are well worth investigating. In this study, a controlled layer-by-layer (LBL) process of encapsulating RIF in biocompatible alginate and chitosan polymers loaded onto Fe3 O4 nanoparticles was developed. Fe3 O4 nanoparticles were synthesized from FeCl3 ·6H2 O using a hydrothermal procedure...
April 2018: Journal of Biomedical Materials Research. Part A
Abdul J Shah, Tamas Kriska, Kathryn M Gauthier, John R Falck, William B Campbell
Angiotensin II (Ang II) and adrenocorticotropic hormone (ACTH) regulate adrenal vascular tone in vitro through endothelial and/or zona glomeulosa cell-derived mediators. The role of these mediators in regulating adrenal blood flow (ABF) and mean arterial pressure (MAP) was examined in anesthetized rats. Ang II (0.01-100 ng/kg) increased ABF (maximal increase of 97.2 ± 6.9 perfusion units (PU) at 100 ng/kg) and MAP (basal, 115 ± 7 mm Hg; Ang II, 163 ± 5 mm Hg). ACTH (0.1-1000 ng/kg) also increased ABF (maximum increase of 91...
November 13, 2017: Endocrinology
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