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Acyclic nucleoside phosphonates: a study on cytochrome P450 gene expression

ABSTRACT: Focused on the cytochromes P450 (CYPs), we studied gene expression changes in mice treated with acyclic nucleoside antivirals adefovir and tenofovir. Positive control group was treated by prototypic CYP inducers phenobarbital and beta-naphthoflavone. Expression profiling with Steroltalk cDNA arrays revealed major changes in CYP mRNA expression in the inducers-treated group but only minor changes in CYP expression in the adefovir and tenofovir groups. 3 groups representing treatments with adefovir, tenofovir and phenobarbital + beta-naphthoflavone. 4-5 animals in each group + a dye swap. Pooled samples from 10 animals treated with saline was used as a reference. Daily application of antivirals for three days, samples were collected after 24 hours from the last treatment.

ORGANISM(S): Mus musculus

SUBMITTER: Peter Juvan

PROVIDER: E-GEOD-47698 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Acyclic nucleoside phosphonates: a study on cytochrome P450 gene expression

Project description:Focused on the cytochromes P450 (CYPs), we studied gene expression changes in mice treated with acyclic nucleoside antivirals adefovir and tenofovir. Positive control group was treated by prototypic CYP inducers phenobarbital and beta-naphthoflavone. Expression profiling with Steroltalk cDNA arrays revealed major changes in CYP mRNA expression in the inducers-treated group but only minor changes in CYP expression in the adefovir and tenofovir groups.

2014-06-03 | GSE47698 | GEO

Beta-naphthoflavone treated worms

Project description:The soil nematode Caenorhabditis elegans is one of the simplest animals having the status of a laboratory model. Its genome contains 80 cytochrome P450 genes (CYP). In order to study CYP gene expression in C. elegans mixed stages and synchronized hermaphrodites were exposed to 18 known xenobiotic cytochrome P450 inducers. Messenger RNA expression was detected by DNA arrays and semiquantitative RT-PCR. Using subfamily-specific primers, a pooled set of exon-rich CYP fragments could be amplified. In this way it was possible to systematically check the influence of different inducers on CYP expression at the same time. The well-known CYP1A inducers beta-naphthoflavone, PCB52, and lansoprazol were the most active and in particular they strongly induced almost all CYP35 isoforms. A few number of further CYP forms were found to be inducible by other xenobiotics like phenobarbital, atrazine, and clofibrate. In addition, a transgenic C. elegans line expressing GFP under control of the CYP35A2 promoter showed a strong induction of the fusion by beta-naphthoflavone in the intestine. Copyright 2001 Academic Press. Set of arrays organized by shared biological context, such as organism, tumors types, processes, etc. Computed

2005-11-25 | E-GEOD-3680 | biostudies-arrayexpress

Beta-naphthoflavone treated worms

2005-11-26 | GSE3680 | GEO

Diet and phenobarbital affect cholesterol homeostasis and drug metabolism

Project description:High cholesterol diet and xenobiotic treatment induce changes in cholesterol homeostasis and drug metabolism. Mice were either 7 days on high cholesterol diet or were treated with phenobarbital. Liver samples were analyzed using Sterolgene v0 cDNA microarrays. Sterolgene microarray is a tool designed to enable focused studies of cholesterol homeostasis and drug metabolism. We show that one week of cholesterol diet down-regulates cholesterol biosynthesis and up-regulates xenobiotic metabolism (Cyp3 family). Phenobarbital treatment also up-regulates xenobiotic metabolism (Cyp2b and Cyp3a families). We can conclude that the Sterolgene series of cDNA microarrays represent novel original tool, enabling focused and cost-wise studies of cholesterol homeostasis and drug metabolism. Keywords: Treatment and diet effects One group of mice was treated i.p. with 50 mg/kg of phenobarbital in vehicle (5% DMSO in corn oil). Untreated group was injected vehicle. Third group was 7 days on 1 % (w/w) cholesterol diet prior vehicle treatment. After 10 h animals were sacrificed and livers were stored. Pools of total RNA from two animals were mixed. Three pools of untreated and phenobarbital treated groups, and two pools of cholesterol diet group were co-hybridized with liver reference on Sterolgene v0 cDNA microarray. No dye-swaps were performed.

2010-05-25 | E-GEOD-6447 | biostudies-arrayexpress

Effect of phenobarbital on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis

Project description:The nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor) mediate the effects of phenobarbital (PB) on gene transcription. To investigate the relative role of CAR and PXR in the induction response, cDNA arrays were generated containing 120 genes which are known to be regulated with these or related nuclear receptors (genes involved in drug metabolism, cholesterol biosynthesis, sterol synthesis/transport, heme synthesis). Samples from livers of wild type and CAR-/-, PXR-/- or CAR/PXR-/- knockout mice were tested after treatment with PB for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments unexpectedly revealed that if CAR and PXR are deleted, PB increases the expression of several other nuclear receptors and genes involved in drug metabolism and cholesterol biosynthesis. Animals were injected i.p. 100mg/kg phenobarbital or vehicle (5% DMSO in corn oil). After 12h they were sacrificed and total RNA was isolated from the livers. Pools of untreated samples were mixed in each genetic variant group (wild type and CAR-/-, PXR-/- or CAR/PXR-/-) with the phenobarbital treated ones and hybridized to Sterolgene V1 arrays.

2008-08-23 | E-GEOD-12489 | biostudies-arrayexpress

Phenobarbital and TCPOBOP effects on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis

Project description:This SuperSeries is composed of the following subset Series: GSE12489: Effect of phenobarbital on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis GSE12509: Effect of TCPOBOP on CAR and PXR regulated genes involved in drug metabolism and cholesterol homeostasis Refer to individual Series

2008-08-23 | E-GEOD-12529 | biostudies-arrayexpress

Xenobiotic response in Drosophila melanogaster: sex dependence of P450 and GST gene induction

Project description:The effect of xenobiotics (phenobarbital and atrazine) on the expression of Drosophila melanogaster CYP genes encoding cytochromes P450, a gene family generally associated with detoxification, was analyzed by DNA microarray hybridization and verified by real time RT-PCR in adults of both sexes. Only a small subset of the 86 CYP genes was significantly induced by the xenobiotics. Eleven CYP genes and three GST genes were significantly induced by phenobarbital, seven CYP and one GST gene were induced by atrazine. Cyp6d5, Cyp6w1, Cyp12d1 and the ecdysone-inducible Cyp6a2 were induced by both chemicals. The constitutive expression of several of the inducible genes (Cyp6a2, Cyp6a8, Cyp6d5, Cyp12d1) was higher in males than in females, and the induced level similar in both sexes. Thus, the level of induction was consistently higher in females than in males. The female-specific and hormonally-regulated yolk protein genes were significantly induced by phenobarbital in males and repressed by atrazine in females. Our results suggest that the numerous CYP genes of Drosophila respond selectively to xenobiotics, providing the fly with an adaptive response to chemically adverse environments. The xenobiotic-inducibility of some CYP genes previously associated with insecticide resistance in laboratory-selected strains (Cyp6a2, Cyp6a8, Cyp12d1) suggests that deregulation of P450 gene expression may be a facile way to achieve resistance. Our study also suggests that xenobiotic-induced changes in P450 levels can affect insect fitness by interfering with hormonally-regulated networks. Keywords: induction by phenobarbital and atrazine in adults drosophila melanogaster of both sex.

2006-06-29 | GSE5125 | GEO

Effect of TCPOBOP and PCN in combination with high-cholesterol diet on genes involved in cholesterol homeostasis

Project description:TCPOBOP (1,4-bis[2-(3,5-dichloropyridyloxy)]benzene) and PCN (pregnenolone 16Î±-carbonitrile) are inducers of drug metabolism through activation of nuclear receptors CAR (constitutive androstane receptor) and PXR (pregnane X receptor), respectively. Mouse experiment was designed to study the effect of CAR and PXR activation on cholesterol homeostasis genes and other genes, which are present on the Steroltalk v2 microarray. Treatments were combined with standard and high-cholesterol diet to observe the interference of high liver cholesterol on nuclear receptor transcription regulation. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Results form these experiments give new knowledge about involvement of âxenosensorsâ CAR and PXR in regulation of endogenous liver metabolism. Animals were injected i.p. 3mg/kg TCPOBOP, 40 mg/kg PCN or vehicle (corn oil) in combination of one week of standard or 1% cholesterol diet prior tretament. After 24h they were sacrificed and total RNA was isolated from the livers. Each sample was hybridized with a reference sample to Steroltalk v2 microarrays.

2010-10-08 | E-GEOD-13688 | biostudies-arrayexpress

Hepatotoxicity

Project description:This SuperSeries is composed of the following subset Series: GSE40336: Effect of Acetominophen on Rat Primary Hepatocytes. GSE40337: Effect of Dioctyl Phthalate on Rat Primary Hepatocytes. GSE40338: Effect of Sodium Valproate on Rat Primary Hepatocytes. GSE40339: Effect of Phenobarbital on Rat Primary Hepatocytes. GSE40340: Effect of Beta-Naphthoflavone on Rat Primary Hepatocytes. GSE40341: Effect of Chlorpromazine HCl on Rat Primary Hepatocytes. GSE40342: Effect of Diisononyl Phthalate on Rat Primary Hepatocytes. GSE40344: Effect of Clofibrate on Rat Primary Hepatocytes. GSE40346: Effect of WY-14643 on Rat Primary Hepatocytes. GSE40347: Effect of Methapyrilene on Rat Primary Hepatocytes. Refer to individual Series

2012-08-28 | E-GEOD-40348 | biostudies-arrayexpress

RNA-seq of Daphnia magna exposed to prochloraz in a 3-generation experiment

Project description:For most chemicals, environmental toxicity is only investigated for a single generation. In this study we investigate the effect of the fungicide prochloraz across generations in Daphnia magna. The study design included two exposure scenarios; one where all three generations were continuously exposed to prochloraz (100 ug/L) and one where only the first generation (F0) was exposed. We studied effects at different levels of biological organization combining key phenotypic effects, such as growth and reproduction, CYP enzyme activity, metabolomics and for generation F2 also transcriptomics

2020-12-01 | E-MTAB-9309 | biostudies-arrayexpress

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