Search results for "Metabolic Detoxication"
showing 7 items of 7 documents
Coordinated induction of drug transporters and phase I and II metabolism in human liver slices
2008
Although regulation of phase I drug metabolism in human liver is relatively well studied, the regulation of phase II enzymes and of drug transporters is incompletely characterized. Therefore, we used human liver slices to investigate the PXR, CAR and AhR-mediated induction of drug transporters and phase I and II metabolic enzymes. Precision-cut human liver slices were incubated for 5 or 24 h with prototypical inducers: phenobarbital (PB) (50 mu M) for CAR, beta-naphthoflavone (BNF) (25 mu M) for AhR, and rifampicin (RIF) (10 mu M) for PXR, and gene expression of the phase I enzymes CYP1A1, 1A2, 3A4, 3A5, 2136, 2A6, the phase II enzymes UGT1A1 and 1A6, and the transporters MRP2, MDR1, BSEP, …
Drug-metabolizing enzymes in the skin of man, rat, and pig.
2007
The mammalian skin has long been considered to be poor in drug metabolism. However, many reports clearly show that most drug metabolizing enzymes also occur in the mammalian skin albeit at relatively low specific activities. This review summarizes the current state of knowledge on drug metabolizing enzymes in the skin of human, rat, and pig, the latter, because it is often taken as a model for human skin on grounds of anatomical similarities. However only little is known about drug metabolizing enzymes in pig skin. Interestingly, some cytochromes P450 (CYP) have been observed in the rat skin which are not expressed in the rat liver, such as CYP 2B12 and CYP2D4. As far as investigated most d…
Biomonitoring of Enniatin B1 and Its Phase I Metabolites in Human Urine: First Large-Scale Study
2020
Enniatins (Enns) are mycotoxins produced by Fusarium spp. which are a fungus widely spread throughout cereals and cereal-based products. Among all the identified enniatins, Enn B1 stands as one of the most prevalent analogues in cereals in Europe. Hence, the aim of this study was to evaluate for the first time the presence of Enn B1 and its phase I metabolites in 300 human urine samples using an ultrahigh-performance liquid chromatography high resolution mass spectrometry (UHPLC-Q-Orbitrap HRMS) methodology. Enn B1 was detected in 94.3% of samples ranging from 0.007 to 0.429 ng/mL (mean value: 0.065 ng/mL). In accordance with previous in vitro and in vivo analysis, hydroxylated metabolites …
Chronic quercetin feeding decreases plasma concentrations of salicylamide phase II metabolites in pigs following oral administration.
2011
We investigated acute effects and effects after chronic intake of the orally administered flavonol quercetin on pharmacokinetics of salicylamide metabolites (SAM) after oral administration of salicylamide in pigs. Salicylamide (8 mg/kg body weight) was orally administered to seven pigs either without or with quercetin (10 mg/kg body weight). Additionally, salicylamide was administered to five pigs that had received a diet supplemented with the flavonol for 1 week. Daily quercetin intake was 10 mg/kg in these animals. Co-ingestion of quercetin with the drug did not alter area under the concentration-time curve (AUC(0→∞)), time to achieve maximum plasma concentration (t(max)), mean residence …
Effects of typical inducers on olfactory xenobiotic-metabolizing enzyme, transporter, and transcription factor expression in rats.
2010
International audience; Several xenobiotic-metabolizing enzymes (XMEs) have been identified in the olfactory mucosa (OM) of mammals. However, the molecular mechanisms underlying the regulation of these enzymes have been little explored. In particular, information on the expression of the transcriptional factors in this tissue is quite limited. The aim of the present study was to examine the impact of five typical inducers, Aroclor 1254, 3-methylcholanthrene, dexamethasone, phenobarbital, and ethoxyquin, on the activities and mRNA expression of several XMEs in the OM and in the liver of rats. We also evaluated the effects of these treatments on the mRNA expression of transcription factors an…
Opioid metabolism and clinical aspects.
2015
Opioids are are commonly used for the management of acute and chronic pain. Opioids have different physicochemical and pharmacokinetic characteristics, which explain the profound changes in the clinical effect in several clinical conditions. Pharmacokinetics influences the opioid response affecting bioavailability, production of metabolites with residual clinical activity, and elimination. Generality of opioid metabolism and clinical implications for specific opioids in different clinical conditions were reviewed to bridge the gap between pharmacokinetics and clinical response. The knowledge of opioid metabolism is essential, particularly for older and complicated patients who receive multi…
A newin vitroapproach for the simultaneous determination of phase I and phase II enzymatic activities of human hepatocyte preparations
2007
Primary hepatocytes are still the best qualified in vitro system to anticipate drug metabolism in man. Recent advances in hepatocytes cryopreservation have notably increased their use not only for drug metabolism studies, but also for other applications such as cell transplantation. Evaluation of the drug-metabolizing competence of each hepatocytes preparation is needed. To date, the metabolic characterization of hepatocytes preparations relies on the assessment of phase I activities and the role of phase II enzymes receives little attention. A novel approach for the rapid assessment of the metabolic functionality of hepatocytes has been developed. A five-probe cocktail was used to simultan…