Search results for " P4"
showing 10 items of 151 documents
Semi-automatic quantitative RT-PCR to measure CYP induction by drugs in human hepatocytes
2003
An assay has been developed for the quantitative measurement of CYP mRNA content of the major human isoforms (1A1, 1A2, 2A6, 2B6, 2C9, 2C19, 2D6, 2E1, 3A4 and 3A5) in human hepatocytes. The method is based on the conversion of mRNAs into their corresponding cDNAs, followed by PCR amplification using appropriate primers. Making use of appropriate internal and external standards it is possible to estimate changes in CYP mRNA content of hepatocytes. The technique has been standardised to run semi-automatically. This procedure can be used to assess the CYP induction potential of new pharmaceuticals at a pre-clinical stage of development. To this aim, human hepatocytes obtained from functional l…
DNA Modification Induced After Metabolic Activation of the Potent Carcinogen Dibenzo[a, l]pyrene in V79 Chinese Hamster Cells Stably Expressing Singl…
2000
Abstract The polycyclic aromatic hydrocarbon (PAH) dibenzo[a, l]pyrene (DB[a, l]P) has been found to be an environmental pollutant and, considering the available data from rodent bioassays, it represents the most carcinogenic member compound of the class of PAH yet discovered. To sort out the contribution of individual cytochromes P450 (P450) in the metabolic activation of this PAH, V79 cells stably expressing a single P450 isoform were treated with DB[a, l]P or enantiomeric DB[a, l]P-11,12-dihydrodiols (diols). Subsequent analysis of the DNA adducts formed revealed substantial differences in the adduct pattern and the total DNA binding depending on the cell line used. Human P450 1B1 effect…
Constitutive and inducible expression of CYP enzymes in immortal hepatocytes derived from SV40 transgenic mice
2003
1. The expression of liver-specific transcription factors and cytochrome P450 (CYP) enzymes have been studied in three new hepatocyte-like cell lines derived from SV Delta 202 transgenic mice: AMH-Delta 202 (adult mouse hepatocytes), TAMH-Delta 202 (tumour-derived adult mouse hepatocytes) and NMH-Delta 202 (newborn mouse hepatocytes). 2. mRNA levels of liver-enriched transcription factors such as D-element binding protein (DBP), liver-enriched transcription activating protein (LAP) and the hepatic nuclear factors (HNF) 1, 2 and 3 in all Delta 202 transgenic hepatocyte lines were similar to those in the wild-type liver and in primary mouse hepatocytes. 3. Analysis of basal CYP activities and…
Isoflavonoid-based bone-sparing treatments exert a low activity on reproductive organs and on hepatic metabolism of estradiol in ovariectomized rats
2007
International audience; The use of soy isoflavones is a potential alternative to hormone replacement therapy in post-menopausal bone-loss prevention. Nevertheless, phytoestrogens can target other organs and may disrupt cell proliferation, or could modify endogenous steroid hormone metabolism. These mechanisms could be linked to an increased risk of developing cancer. We therefore studied the possible side effects of such treatments in an experimental model of menopause. Forty adult female Wistar rats were ovariectomized and fed with a genistein-, daidzein- or equol-supplemented diet at bone-sparing levels (10 mg/kg BW/day) for 3 months. The estrogenic effects were assessed by histological a…
Drug-metabolizing enzyme activities in freshly isolated oval cells and in an established oval cell line from carcinogen-fed rats
1994
The activities of several different phase I and phase II drug-metabolizing enzymes were measured in freshly isolated oval cells from rats fed a choline-deficient/DL-ethionine-supplemented diet for 6 weeks and also in vitro in the established oval cell line OC/CDE 6. No cytochrome P450 was spectrophotometrically measurable in both preparations and two cytochrome P450-dependent monoxygenase activities, aminopyrine N-demethylase and ethoxyresorufin O-deethylase, could not be detected in the oval cells of both sources. However, cytosolic glutathione transferase, microsomal epoxide hydrolase and UDP-glucuronosyltransferase activities were clearly measurable in oval cells. Similar enzyme activiti…
Androgen hydroxylation catalysed by a cell line (SD1) that stably expresses rat hepatic cytochrome P-450 PB-4 (IIB1).
1989
Androgen hydroxylation catalysed by Chinese hamster fibroblast SD1 cells, which stably express cytochrome P-450 form PB-4, the rat P450IIB1 gene product, was assessed and compared to that catalysed by purified cytochrome P-450 PB-4 isolated from rat liver. SD1 cell homogenates catalysed the NADPH-dependent hydroxylation of androstenedione and testosterone with a regioselectivity very similar to that purified by P-450 PB-4 (16 beta-hydroxylation/16 alpha-hydroxylation = 6.0-6.8 for androstenedione; 16 beta/16 alpha = 0.9 for testosterone). Homogenates prepared from the parental cell line V79, which does not express detectable levels of P-450 PB-4 or any other cytochrome P-450, exhibited no a…
Pd nanoparticles formation inside porous polymeric scaffolds followed by in situ XANES/SAXS
2015
International audience; Simultaneous time-resolved SAXS and XANES techniques were employed to follow in situ the formation of Pd nanoparticles from palladium acetate precursor in two porous polymeric supports: polystyrene (PS) and poly(4-vinyl-pyridine) (P4VP). In this study we have investigated the effect of the use of different reducing agents (H-2 and CO) from the gas phase. These results, in conjunction with data obtained by diffuse reflectance IR (DRIFT) spectroscopy and TEM measurements, allowed us to unravel the different roles played by gaseous H-2 and CO in the formation of the Pd nanoparticles for both PS and P4VP hosting scaffolds
Transcriptomic Analyses Reveal 2 and 4 Family Members of Cytochromes P450 (CYP) Involved in LPS Inflammatory Response in Pharynx of Ciona robusta
2021
Cytochromes P450 (CYP) are enzymes responsible for the biotransformation of most endogenous and exogenous agents. The expression of each CYP is influenced by a unique combination of mechanisms and factors including genetic polymorphisms, induction by xenobiotics, and regulation by cytokines and hormones. In recent years, Ciona robusta, one of the closest living relatives of vertebrates, has become a model in various fields of biology, in particular for studying inflammatory response. Using an in vivo LPS exposure strategy, next-generation sequencing (NGS) and qRT-PCR combined with bioinformatics and in silico analyses, compared whole pharynx transcripts from naïve and LPS-exposed C. robusta…
Anandamide inhibits IL-12p40 production by acting on the promoter repressor element GA-12: Possible involvement of the COX-2 metabolite prostamide E 2
2007
The eCB [endoCB (cannabinoid)] system is being considered as a novel therapeutic target for immune disorders. Cytokines of the IL-12 (interleukin-12) family have essential functions in cell-mediated immunity. In the present study, we have addressed the mechanisms of action of the eCB AEA (anandamide) on the regulation of IL-12p40 in activated microglia/macrophages. We demonstrated that AEA can inhibit the expression of p35, p19 and p40 subunits, which form the biologically-active cytokines IL-12 and IL-23 in microglia stimulated with LPS (lipopolysaccharide)/IFNγ (interferon γ). Additionally, we have provided evidence that AEA reduces the transcriptional activity of the IL-12p40 gene in LPS…
Effect of oxidative stress on UDP-glucuronosyltransferases in rat astrocytes.
2012
WOS:000309170300003; International audience; The present work reports data regarding effects of an induced oxidative stress on the mainly expressed isoforms of UDP-glucuronosyltransferases (UGTs) in the brain. UGT1A6 and UGT1A7 expression and enzymatic activities toward the 1-naphthol were analyzed in rat cultured astrocytes following the exposure for 48 h to redox-cycling xenobiotic compounds such as quinones and bipyridinium ions. The expression of NADPH:cytochrome P450 reductase and NAD(P)H:quinone oxidoreductase 1 (NQO1) was also investigated. Oxidative stress induced significant deleterious changes in astrocyte morphology, decreased cell viability and inhibited catalytic function of UG…