Search results for "CYP"

Induction of Human P-Glycoprotein in Caco-2 cells: Development of a Highly Sensitive Assay System for P-Glycoprotein-Mediated Drug Transport

2006

The aim of this work is to develop a highly sensitive assay system for P-gp-mediated transport by using two methods, induction of P-gp and short-term culture of Caco-2 cells. To induce P-gp in Caco-2 cells, cells were cultured in vinblastine-containing medium. The mRNA level of P-gp was approximately 7-fold higher in Caco-2 cells cultured with vinblastine (P-gp-induced Caco-2 cells) than in control cells. Western blot analysis showed a significant increase in P-gp expression. After cell differentiation, the mRNA level of P-gp was downregulated, however, P-gp-induced Caco-2 cells still possessed a 5.6-fold higher mRNA level of P-gp compared to control cells. Polarized transport of substrate …

Droplet-to-droplet microarray for drug screening in picoliter scale

2012

The Influence of Single-Dose and Short-Term Administration of Quercetin on the Pharmacokinetics of Midazolam in Humans.

2015

Quercetin is a plant flavonol that is available from both daily diet and nutraceuticals. To investigate the effect of acute and short-term intake of high-dose quercetin on CYP3A-mediated metabolism, 10 healthy volunteers received 7.5 mg oral midazolam without, with a single dose of 1500 mg quercetin and after 1-week supplementation with 1500 mg quercetin daily. A substudy was performed in three subjects to explore the impact of repeated quercetin intake on intravenously administered midazolam. Coadministration with a single dose of quercetin did not significantly alter the pharmacokinetics of midazolam and its 1'-hydroxymetabolite, but following short-term quercetin intake, there was a tren…

CYP3 phylogenomics: evidence for positive selection of CYP3A4 and CYP3A7.

2008

CYP3A metabolizes 50% of currently prescribed drugs and is frequently involved in clinically relevant drug interactions. The understanding of roles and regulations of the individual CYP3A genes in pharmacology and physiology is incomplete.Using genomic sequences from 16 species we investigated the evolution of CYP3 genomic loci over a period of 450 million years.CYP3A genes in amniota evolved from two ancestral CYP3A genes. Upon the emergence of eutherian mammals, one of them was lost, whereas, the other acquired a novel genomic environment owing to translocation. In primates, CYP3A underwent rapid evolutionary changes involving multiple gene duplications, deletions, pseudogenizations, and …

Frontiers of metal-coordinating drug design

2020

INTRODUCTION: The occurrence of metal ions in biomolecules is required to exert vital cellular functions. Metal-containing biomolecules can be modulated by small-molecule inhibitors targeting their metal-moiety. As well, the discovery of cisplatin ushered the rational discovery of metal-containing-drugs. The use of both drug types exploiting metal–ligand interactions is well established to treat distinct pathologies. Therefore, characterizing and leveraging metal-coordinating drugs is a pivotal, yet challenging, part of medicinal chemistry. AREA COVERED: Atomic-level simulations are increasingly employed to overcome the challenges met by traditional drug-discovery approaches and to compleme…

Fast Regulation of Cytochrome P450 Activities by Phosphorylation and Consequences for Drug Metabolism and Toxicity

2002

In contrast to the well-known regulation of cytochrome P450 (CYP) activity by enzyme induction, which represents a process with slow onset and slow offset, more recent studies revealed phosphorylation as a fast (within observation instantaneous) and isoenzyme-selective regulation. The phosphorylated enzyme (investigated isozyme: CYP2B1) was fully inactive. The phosphorylation is mediated by PKA and hence under control of hormones and drugs that alter cellular cAMP levels. The consequences for the metabolic control of toxic species derived from drugs and environmental carcinogens are discussed. This information will help to improve therapy with drugs metabolized by CYPs which are phosphoryla…

Interspecific and intraspecific interactions in the monogenean communities of fish: a question of study scale?

2007

SUMMARYMonogenean communities of fish have generally been considered non-interactive as negative interspecific interactions have rarely been reported. Most of the earlier studies on monogenean communities, however, have been conducted not only in systems with relatively low parasite abundances but, more importantly, at study scales where microhabitat-level interactions between the parasites are easily overlooked. We examined the communities of 3 abundant Dactylogyrus (Monogenea) species on the gills of crucian carp (Carassius carassius) by analysing the interactions at the scale of individual gill filaments, where interactions between the species, if any, should most likely take place. Cont…

Seasonal response of vegetation on pollutants removal in constructed wetland system treating dairy wastewater

2022

Constructed wetland systems provide the ideal solution for small and medium dairy farms as they can be built close to the farm and are easy to manage and use. However, their perfomance is significantly affected by vegetation activity during the year. The aims of the present study were to assess the treatment of dairy wastewater (DWW) by a horizontal subsurface flow system (HSSFs) and the effect of plants in the removal efficiency (RE) of BOD5, COD, total N (TN) and total P (TP), in Sicily (Italy). The HSSFs treated 6/7 m3 per day of wastewater produced by a small dairy farm subsequent to biological treatment. The system included two units which were separately planted with Arundo donax L. a…

Fatty acid metabolism, pharmacological nutrients and hypertension.

1997

Abstract The purpose of the present study was to investigate the effect of a concentrated preparation (EPA30) containing eicosapentaenoic acid (EPA. 20:5 n -3) and docosahexaenoic acid (DHA, 22:6 n -3) on the limiting desaturation steps of the polyunsaturated fatty acid biosynthesis in spontaneously hypertensive rats (SHR). Adult SHR were divided into two groups: one group received a standard diet, and the experimental group the standard diet including 0.8% of EPA30 for 9 weeks. Blood pressure was measured at the end of the diets. The desaturase activities and fatty acid composition were determined in isolated hepatocytes. The blood pressure did not decrease in the experimental group. The d…

2002

We carried out enclosure experiments to assess the potential deleterious effects of the alien species common carp (Cyprinus carpio L.), mosquitofish (Gambusia holbrookii Gir.), and pumpkinseed sunfish (Lepomis gibbosus L.) on water quality and food web in a severely degraded floodplain wetland, the Spanish National Park Las Tablas de Daimiel. With addition of either carp or pumpkinseed sunfish, chlorophyll a and turbidity levels, as well as concentrations of total phosphorus and total nitrogen increased. The magnitude of this increase depended on fish species and was severest in the carp treatment. Mosquitofish did not significantly affect water quality. In the treatments with fish, cyclopo…