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Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis

ABSTRACT: The aim of the study was to see any effect of rosuvastatina or atorvastatin on cholesterol homeostasis after 24 hours in C57BL/6 hyperlipidemic mice (induced by diet). Experiments were perfomed using a custom Steroltalk v2 microarray. Effect of both statins on drug metabolism was also evaluated. All experiments were done within the European sixth Framework program “Steroltalk” (www.steroltalk.net).

ORGANISM(S): Mus musculus

PROVIDER: GSE13689 | GEO | 2009/11/20

SECONDARY ACCESSION(S): PRJNA114575

REPOSITORIES: GEO

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Effect of rosuvastatin and atorvastatin in combination with high-cholesterol diet on cholesterol homeostasis

Project description:The aim of the study was to see any effect of rosuvastatina or atorvastatin on cholesterol homeostasis after 24 hours in C57BL/6 hyperlipidemic mice (induced by diet). Experiments were perfomed using a custom Steroltalk v2 microarray. Effect of both statins on drug metabolism was also evaluated. All experiments were done within the European sixth Framework program âSteroltalkâ (www.steroltalk.net). Animals were given one peroral application of vehicle (tap water), 20 mg/kg rosuvastatin or 40 mg/kg atorvastatin after one week of 1% cholesterol diet. 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.

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Atorvastatin, rosuvastatin and rifampicin effect on human primary hepatocyte transcriptome [Steroltalk platform]

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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 16α-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 “Steroltalk” (www.steroltalk.net). Results form these experiments give new knowledge about involvement of ‘xenosensors’ CAR and PXR in regulation of endogenous liver metabolism.

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Project description:The nuclear receptor PXR (Pregnane X rreceptor) mediates the effects of pregnenolone-16alpha-carbonitrile (PCN) on gene transcription. The relative role of PXR and also CAR to the induction response by PCN was studied on cDNA arrays containing 320 (Steroltalk V2) genes (genes involved in cyrcadian rhythm, 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 PCN for gene expression within the European Framework V program “Steroltalk” (www.steroltalk.net). Results from these experiments show the complex role of PXR receptor in the expression of genes involved in cyrcadian rhythm, drug metabolism and cholesterol biosynthesis.

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