Dose and temporal effects of Phenobarbital on the liver miRNAome of male Fischer rats
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Nigel Gooderham
PROVIDER: E-GEOD-48489 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
Similar Datasets
Project description:Male Fischer rats were fed a control diet or a diet supplemented with 50, 500 or 1000 ppm Phenobarbital. The 500 and 1000 ppm PB doses induced a transient hyperplasia and a sustained hepatomegaly in treated animals. The animals were sacrificed and liver miRNAome was profiled in three animals per group after 1, 3, 7, and 14 days of treatment. The aim was to investigate the time and dose dependent effects of phenobarbital treatment on the liver miRNAome
2013-07-03 | GSE48489 | GEO
Project description:Here, we examined the liver microRNA profile of male Fischer rats exposed through their diet to genotoxic (2-acetylaminofluorene) and epigenetic (phenobarbital, diethylhexylphthalate, methapyrilene HCL, monuron, and chlorendic acid) chemical hepatocarcinogens, as well as to non-hepatocarcinogenic treatments (benzophenone, and diethylthiourea) for three months. The aim of the study was to investigate how liver miRNA profiles relate to mode of action and carcinogenic potential of chemicals. In total miRNA profiles from 38 liver samples were examined. These included 3-5 samples for animal fed control diets or diet supplemented with designated chemicals. For each chemical a carcinogenic or a maximum tolerated dose was chosen based on published literature. The treatments were Diethylthiourea (DETU) 2500 ppm; Benzophenone (BP) 1250 ppm ; Monuron (MON) 1500 ppm ; Diethylhexylphthalate (DEHP) 12000 ppm ; Phenobarbital (PB) 1000 ppm; Chlorendic acid (CA) 1250 ppm; Methapyrilene HCl (MP) 250 ppm; 2-Acetyl aminofluorene (2-AAF) 40 ppm.
2013-07-03 | E-GEOD-48492 | biostudies-arrayexpress
Project description:This SuperSeries is composed of the SubSeries listed below. Male CD-1 mice and WH rats (4 animals/dose) were fed diets containing 0 (control) or 2500 ppm NaPB for 7 days. Male chimeric mice (4-5 animals/dose) also fed diets containing 0 (control) or 1000 ppm NaPB for 7 days. Liver samples were used for gene expression analysis.
2014-08-29 | E-GEOD-57058 | biostudies-arrayexpress
Project description:MicroRNAs (miRNAs) are critical regulators of gene expression, yet much remains unknown regarding miRNA changes resulting from environmental exposures and whether they influence pathway signaling across various tissues and time. To gain knowledge on these novel topics, we set out to investigate in vivo miRNA responses to inhaled formaldehyde, an important air pollutant known to disrupt miRNA expression profiles. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde (6 hours/day) for 7 days, 28 days, or 28 days followed by a 7 day recovery. Genome-wide miRNA expression profiles and associated signaling pathways were assessed within the nasal respiratory mucosa, circulating mononuclear white blood cells (WBC), and bone marrow (BM). Male Fischer rats received nose-only inhalation exposures of 2 ppm formaldehyde. Three exposure durations were investigated: (1) 2 ppm formaldehyde exposure, 6 hours/day, for 7 days (7-day group), (2) 2 ppm formaldehyde exposure, 6 hours/day, for 28 days (28-day group), and (3) 2 ppm formaldehyde exposure, 6 hours/day, for 28 days, with a 7 day recovery period following the last exposure (28-day plus recovery group). Control (unexposed) rats were placed in nose-only exposure tubes containing room air for the same duration. After the last exposure period (or the last recovery period for the 28-day plus recovery group), animals were euthanized. RNA were assessed from sampes collected from the nasal epithelium, circulating white blood cells, and bone marrow cells. Genome-wide miRNA expression profiles were evaluated using microarrays.
2014-01-07 | E-GEOD-42393 | biostudies-arrayexpress
Project description:In addition to gaining knowledge on in vivo miRNA responses to formaldehyde, we set out to relate these miRNA responses to transcriptional profiles modified by formaldehyde. Rats were exposed by inhalation to either 0 or 2 ppm formaldehyde (6 hours/day) for 28 days. Genome-wide transcriptional profiles and associated signaling pathways were assessed within the nasal respiratory mucosa and circulating mononuclear white blood cells (WBC). Male Fischer rats received nose-only inhalation exposures of 2 ppm formaldehyde for 7 days or 28 days (6 hours/day). Control (unexposed) rats were placed in nose-only exposure tubes containing room air for the same duration. After the last exposure period, animals were euthanized. RNA were assessed from sampes collected from the nasal epithelium and circulating white blood cells. Genome-wide mRNA expression profiles were evaluated using microarrays.
2014-01-07 | E-GEOD-42394 | biostudies-arrayexpress
Project description:High doses of sodium phenobarbital (NaPB), a constitutive androstane receptor (CAR) activator, have been shown to produce hepatocellular tumors in rodents by a mitogenic mode of action (MOA) involving CAR activation. The effect of 1 week dietary treatment with NaPB on liver weight and histopathology, hepatic CYP2B enzyme activity and CYP2B/3A mRNA expression, replicative DNA synthesis and selected genes related to cell proliferation and functional transcriptomic and metabolomic analyses was studied in male CD-1 mice, Wistar Hannover (WH) rats and chimeric mice with human hepatocytes. The treatment of chimeric mice with 1000-1500 ppm NaPB resulted in plasma levels around 3-5 fold higher than those observed in human subjects given therapeutic doses of NaPB. NaPB produced dose-dependent increases in hepatic CYP2B activity and CYP2B/3A mRNA levels in all animal models. Integrated functional metabolomic and transcriptomic analyses demonstrated the responses to NaPB in human liver were clearly different from those in rodents. While NaPB produced a dose-dependent increase in hepatocyte replicative DNA synthesis in CD-1 mice and WH rats, no increase in replicative DNA synthesis was observed in human hepatocyte-originated areas of chimeric mice. In addition, treatment with NaPB had no effect on Ki-67, PCNA, GADD45β, and MDM2 mRNA expression in chimeric mice, whereas significant increases were observed in CD-1 mice and/or WH rats. Thus, while NaPB could activate CAR in rodent and human hepatocytes, NaPB did not increase replicative DNA synthesis in human hepatocytes of chimeric mice, whereas it was mitogenic to rat and mouse hepatocytes. As human hepatocytes are refractory to the mitogenic effects of NaPB, the MOA for NaPB-induced rodent liver tumor formation is thus not relevant for humans. Male WH rats (4 animals/dose) were fed diets containing 0 (control) or 2500 ppm NaPB for 7 days. Liver samples were used for gene expression analysis.
2014-08-29 | E-GEOD-57057 | biostudies-arrayexpress
Project description:Expression profile of liver of ICR mice (13-week old) treated with control diet (CRF-1) or CRF-1 containing 500 ppm diosgenin for 4 weeks. Nine-week old ICR mice were fed with a basal diet (CRF-1) or that containing 500 ppm diosgenin for 4 weeks ad libitum (n = 3 in each group). Food intake and body weight were measured on a weekly basis for the duration of the study.
2010-10-08 | E-GEOD-24580 | biostudies-arrayexpress
Project description:Drug addiction is a chronic relapsing brain disease. The alterations of glucose uptake and metabolism were found in the brain of drug addicts. Insulin mediates brain glucose metabolism and its abnormality could induce brain injury and cognitive impairment. Here, we established a rat model of phenobarbital addiction by 90 days dosed escalation and evaluated addiction-related symptoms. We also performed proteomic analysis of the function of the differentially expressed (DE) proteins via bioinformatics in brain tissues by LC-MS/MS on day 60 and 90 of phenobarbital or 0,5% CMC-Na (vehicle) administration. The results showed that phenobarbital addictive rats developed severe withdrawal symptoms after abstinence. Proteomics analysis showed that numerous DE proteins were enriched after phenobarbital administration; which CALM1, ARAF and Cbl proteins (related to insulin signaling pathway) were significantly downregulated on day 60 but no day 90; however, SLC27A3 and NF-kB1 proteins (related to insulin resistance) were significantly upregulated on day 90. Our data indicate that insulin signaling pathway and insulin resistance may play a role in the development of phenobarbital addiction and brain injury and the findings may have important clinical implication.
2020-10-29 | PXD021101 | Pride
Project description:This study evaluated transcriptional effects of the lung carcinogen NNK ( 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone) injection and selenocystine consumption on the murine lung. Female A/J mice at 5 weeks of age were obtained from The Jackson Laboratory. Animals were stabilized on an unsupplemented AIN-76 diet for one week prior to being given the selenium supplemented diet. The basal level of selenium in the diet is 0.35 ppm Se, the selenocytine supplemention was at 15 ppm. NNK was administered i.p. as a single 10 uM injection in 0.2 mL saline. With this protocol, 100% of animals reproducibly develop lung tumors after 3 months. Three days after NNK administration, animals were provided AIN-76A diets supplemented with selenocystine at 15 ppm selenium ad libitum for 10 days. Animals were sacrificed thirteen days after NNK administration. Lung tissue was harvested, immediately homogenized in Trizol and frozen. The organic extracted RNAs were run over Qiagen RNeasy columes before quantifying and qualifying them. All samples had RNA quality index's greater than 9. Four groups of A/J mice were utilized with 4 biological replicates per group. 1) Untreated - controls on the AIN-76 diet (0.35 ppm Se). 2) NNK treated - single injection of NNK, maintained on norma AIN-76 diet, sacraficed after 13 days. 3) SECY - selenocystine supplemented (15 ppm) for 10 days on a AIN-76 diet then sacraficed. 4) NNK plus SECY - single injection of NNK, after 3 days, selenocystine supplemented (15 ppm) diet for 10 days then sacraficed. RNAs from the the four untreated mice were combined to phenotypically anchor the dual color expression profile. mouse lung responses to NNK injection and/or selenocystine dietary supplementation
2012-05-31 | E-GEOD-29447 | biostudies-arrayexpress
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