West Virginia Chemical Spill
Ontology highlight
ABSTRACT:
ORGANISM(S): Rattus norvegicus
SUBMITTER: Scott Auerbach
PROVIDER: E-GEOD-75658 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of propylene glycol phenyl etherl in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 49 samples were evaluated in this study. 25 were from liver and 24 were from kidney. Five biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 4 biological replicates. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75656 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of crude 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 44 samples were evaluated in this study. 27 were from liver and 17 were from kidney. Signficant batch effects were detected with a subset of samples and these were removed from the study prior to data analysis and are therefore not included in this GEO series. 3 (kidney) or 4 (liver) biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 2-4 biological replicates. The groups that contain only 2 or 3 replicates do so due to a number of samples not passing QC as byproduct of batch effects. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75655 | biostudies-arrayexpress
Project description:The goal of this study was to characterize the potential toxicity and genomic benchmark dose of 4-methylcyclohexylmethanol in liver and kidney of male Harlan Sprague Dawley rats using a 5 day dose-response toxicogenomics study design. The 5 day study is used to quickly identify the dose levels where changes in molecular pathways occur. These dose level where pathway level effects begin to occur have been shown to provide a close approximation of a no effect dose level from more resource intensive guideline toxicological assessments. A total of 58 samples were evaluated in this study. 29 were from liver and 29 were from kidney. Five biological replicate were obtained for the 0 mg/kg/day control group for both liver and kidney. All other non-zero dose groups contain 4 biological replicates. The control groups for liver and kidney are the 0 mg/kg dose groups for those organs.
2015-12-31 | E-GEOD-75657 | biostudies-arrayexpress
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 34 testis samples were analyzed. Seven biological replicates for control, 4 biological replicates for mid dose myclobutanil, 5 biological replicates for high dose myclobutanil, 4 biological replicates for mid dose propiconazole, 5 biological replicates for high dose propiconazole, 4 biological replicates for mid dose triadimefon, and 5 biological replicates for high dose triadimefon.
2008-04-09 | E-GEOD-10412 | biostudies-arrayexpress
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver and testis from Wistar Han IGS rats fed myclobutanil (M: 500, 2000 ppm), propiconazole (P: 500, 2500 ppm), or triadimefon (T: 500, 1800 ppm) from gestation day six to postnatal day 92. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Triadimefon induced a distinctive expression profile of genes involved in liver sterol biosynthesis. There were no common pathways modulated by all three triazoles in the testis. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism (Aldh1a1, Cyp1a1, Cyp2b2, Cyp3a1, Slco1a4, Udpgtr2), fatty acid metabolism (Cyp4a10, Pc, Ppap2b), and steroid metabolism (Srd5a1, Ugt1a1, Ugt2a1) were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism, sterol biosynthesis, and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 35 liver samples were analyzed. Seven biological replicates for the controls, 5 biological replicates for mid dose myclobutanil and 5 biological replicates for high dose mylcobutanil. There are 5 biological replicates for mid dose propiconazole, 4 biological replicates for high dose propiconazole, 5 biological replicates for mid dose triadimefon, and 4 biological replicates for triadimefon.
2008-04-09 | E-GEOD-10411 | biostudies-arrayexpress
Project description:The triazole antifungals myclobutanil (MYC), propiconazole (PPZ) and triadimefon (TDF) all disrupt steroid hormone homeostasis and cause varying degrees of hepatic toxicity. To identify biological pathways consistently activated across various study designs, gene expression profiling was conducted on livers from rats following acute, repeated dose, or prenatal to adult exposures. To explore conservation of responses across species, gene expression from these rat in vivo studies were also compared to in vitro data from rat and human primary hepatocytes exposed to MYC, PPZ, or TDF. Pathway and gene level analyses across time of exposure, dose, and species identified patterns of expression common to all three triazoles, which were also conserved between rodents and humans. Pathways affected included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Many of the differentially expressed genes are regulated by the nuclear receptors CAR, PPAR alpha and PXR, including ABC transporter genes (Abcb1 and MDR1), genes significant to xenobiotic, fatty acid, sterol and steroid metabolism (Cyp2b2 and CYP2B6; Cyp3a1 and CYP3A4; Cyp4a22 and CYP4A11) and xxx (Ugt1a1 and UGT1A1). Modulation of hepatic sterol and steroid metabolism is a plausible mechanism for triazole induced increases in serum testosterone. The gene expression changes caused by all three triazoles appear to focus on pathways regulating lipid and testosterone homeostasis, identifying potential common mechanisms of triazole hepatotoxicity that are conserved between rodents and humans. Experiment Overall Design: A total of 35 samples were analyzed. Three biological replicates for the controls (DMSO 0.1%), 2 biological replicates for positive control PCN, 3 biological replicates for positive control phenobarbital, 3 biological replicates for low dose myclobutanil, 3 biological replicates for mid dose myclobutanil, 3 biological replicates for high dose myclobutanil. Three biological replicates each for low, mid, and high dose propiconazole, and 3 biological replicates each for low, mid, and high dose triadimefon.
2008-06-16 | E-GEOD-9387 | biostudies-arrayexpress
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day), propiconazole (300 mg/kg/day), or triadimefon (175 mg/kg/day) for 72 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 12 liver samples were analyzed. Three biological replicates each for the controls, 300 mg/kg/day myclobutanil, 300 mg/kg/day propiconazole, and 175 mg/kg/day triadimefon.
2008-04-08 | E-GEOD-10409 | biostudies-arrayexpress
Project description:The triazole antifungals myclobutanil (MYC), propiconazole (PPZ) and triadimefon (TDF) [Propiconazole CASNR 60207-90-1; Triadimefon CASNR 43121-43-3; Myclobutanil CASNR 88671-89-0] all disrupt steroid hormone homeostasis and cause varying degrees of hepatic toxicity. To identify biological pathways consistently activated across various study designs, gene expression profiling was conducted on livers from rats following acute, repeated dose, or prenatal to adult exposures. To explore conservation of responses across species, gene expression from these rat in vivo studies were also compared to in vitro data from rat and human primary hepatocytes exposed to MYC, PPZ, or TDF. Pathway and gene level analyses across time of exposure, dose, and species identified patterns of expression common to all three triazoles, which were also conserved between rodents and humans. Pathways affected included androgen and estrogen metabolism, xenobiotic metabolism signaling through CAR and PXR, and CYP mediated metabolism. Many of the differentially expressed genes are regulated by the nuclear receptors CAR, PPAR alpha and PXR, including ABC transporter genes (Abcb1 and MDR1), genes significant to xenobiotic, fatty acid, sterol and steroid metabolism (Cyp2b2 and CYP2B6; Cyp3a1 and CYP3A4; Cyp4a22 and CYP4A11) and xxx (Ugt1a1 and UGT1A1). Modulation of hepatic sterol and steroid metabolism is a plausible mechanism for triazole induced increases in serum testosterone. The gene expression changes caused by all three triazoles appear to focus on pathways regulating lipid and testosterone homeostasis, identifying potential common mechanisms of triazole hepatotoxicity that are conserved between rodents and humans. Experiment Overall Design: A total of 43 samples were analyzed. Four biological replicates for the controls (DMSO 0.1%), 2 biological replicates for positive control Rifampicin CASNR 13292-46-1, 4 biological replicates for positive control Phenobarbital sodium CASNR 57-30-7, 3 biological replicates for low dose myclobutanil, 3 biological replicates for mid dose myclobutanil, 4 biological replicates for high dose myclobutanil. Four biological replicates each for low, mid, and high dose propiconazole, and 4, 4, and 3 biological replicates each for low, mid, and high dose triadimefon, respectively.
2008-04-09 | E-GEOD-10410 | biostudies-arrayexpress
Project description:The modes of triazole reproductive toxicity have been characterized by an observed increased in serum testosterone and reduced insemination and fertility indices. The key events involved in the disruption in testosterone homeostasis and reduced fertility remain unclear. Gene expression analysis was conducted on liver from Sprague Dawley rats dosed with myclobutanil (300 mg/kg/day) or triadimefon (175 mg/kg/day) for 6, 24 or 336 hours. Pathway-based analysis highlighted key biological processes affected by all three triazoles in the liver including fatty acid catabolism, steroid metabolism, and xenobiotic metabolism. Within the pathways identified in the liver, specific genes involved in phase I-III metabolism and fatty acid metabolism were affected by all three triazoles. These modulated genes are part of a network of lipid and testosterone homeostasis pathways regulated by the constitutive androstane (CAR) and pregnane X (PXR) receptors. Gene expression profiles from this study indicate triazoles activate CAR and PXR; increase fatty acid catabolism and steroid metabolism in the liver; constituting a plausible series of key events contributing to the observed disruption in testosterone homeostasis. Experiment Overall Design: A total of 15 liver samples were analyzed. Five biological replicates each for the controls, 225 mg/kg/day myclobutanil, and 175 mg/kg/day triadimefon.
2008-04-09 | E-GEOD-10408 | biostudies-arrayexpress
Project description:Increased COUP-TFII levels are found in human dilated cardiomyopathy as well as in mouse models that develop cardiomyopathy. COUP-TFII overexpression in adult mouse hearts caused ventricular dilation and compromised cardiac functions. To gain insights on COUP-TFII’s effect in hearts, we identified the molecular profile of COUP-TFII overexpressing hearts through microarray analysis. The result may shred light on molecular mechanisms that mediate development of dilated cardiomyopathy. We utilized a previously established CAG-S-COUP-TFII allele and crossed it with the Myh6-MerCreMer (Myh6-MCM) line to overexpress COUP-TFII specifically in cardiomyocytes at two months of age by administration of tamoxifen. The experimental group has genotype of Myh6-MCM; CAG-S-COUP-TFII while the control group consists of Myh6-MCM mice (Figure 1C). Whole ventricles were harvested 16 days post induction for molecular profiling.
2015-07-24 | E-GEOD-63759 | biostudies-arrayexpress