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Carbon tetrachloride and Acetaminophen hepatotoxicity study

ABSTRACT: Differential gene expression in mice liver after carbon tetrachloride and acetaminophen administration. Livers from control mice were compared with drug treated mice livers at different time points. Keywords: Time-course

ORGANISM(S): Mus musculus

PROVIDER: GSE4874 | GEO | 2007/02/27

SECONDARY ACCESSION(S): PRJNA95939

REPOSITORIES: GEO

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Carbon tetrachloride and Acetaminophen hepatotoxicity study

Project description:Differential gene expression in mice liver after carbon tetrachloride and acetaminophen administration. Livers from control mice were compared with drug treated mice livers at different time points. Keywords: Time-course Mice (Mus musculus) belonging to control and carbon tetrachloride and acetaminophen-administered groups (n=4) were sacrificed. The livers were snap frozen in liquid nitrogen, and subsequently stored at -80ÂºC till further use. Liver samples were homogenized and total RNA was extracted with TRI reagent. 25 ug of total RNA was converted into labeled cDNA using CyScribe first strand cDNA labeling kit. The Cy5 and Cy3 labeled cDNAs were resuspended in Cyscribe Hyb buffer containing 10ug/ml sheared Salmon sperm DNA and 10ug/ml Yeast tRNA. The labeled samples were hybridized to the arrays and incubated for 16-18hrs at 42ÂºC. Fluorescent array images were collected for both Cy3 and Cy5 with molecular dynamics III scanner supported with ImageQuant v5.0. Image intensity data were extracted and analyzed with ArrayVision v8.0 analysis software. Background corrected data was LOWESS normalized and log ratios were calculated using Avadis v4. Further, mean log ratios were calculated for duplicate spots. Replicate experiments were carried out in dye swap manner for each time point.

2010-06-11 | E-GEOD-4874 | biostudies-arrayexpress

Discover preclinical biomarkers of hepatotoxicity: Acetaminophen and Carbon tetrachloride

Project description:Preclinical biomarkers useful for identification of idiosyncratic drugs have not been identified. It is hypothesized that patterns of transcript expression for the hepatotoxicants, including classical and idiosyncratic hepatotoxicants, are similar and the patterns differ from those of non-hepatotoxicants. This experiment is part of the biomarkers study, and focus on two clasical hepatotoxicants: Acetaminophen and Carbon tetrachloride. We have employed whole genome microarray expression profiling to identify liver gene expression changes induced by hepatotoxicants. For the same animal, urinary microRNA profiling were analyzed. APAP and CCl4 both significantly increased the urinary levels of 44 and 28 miRNAs, respectively. In addition, 10 of the increased miRNAs were in common between APAP and CCl4. Computational analysis was used to predict target genes of the 10 shared hepatotoxicant-induced miRNAs. From the same animals, liver gene expression profiling was performed using whole genome microarrays. Eight putative target genes were found to be significantly altered in the liver of APAP and CCl4 treated animals. Acetaminophen induced liver gene expression changes in rats (Six to seven week-old male Sprague-Dawley rats, provided by the US Food and Drug Administration National Center for Toxicological Research (NCTR) breeding colonies, were used for the study.) were measured at 6 hours, 24 hours, 3 days and 7 days after exposure to doses of 0, 100 and 1250 mg/kg. Carbon tetrachloride induced liver gene expression changes in rats were measured at 6 hours, 24 hours and 3 days after exposure to doses of 0, 50 and 2000 mg/kg. Each group has at least 4 animals, total of 96 samples.

2012-03-15 | E-GEOD-32891 | biostudies-arrayexpress

Discover preclinical biomarkers of hepatotoxicity: Acetaminophen and Carbon tetrachloride

2012-03-15 | GSE32891 | GEO

Genome-wide analysis of gene expression of livers of wild type and IL-4/IL-13-/- mice after carbon tetrachloride-induced injury

Project description:Global analysis of differentially expressed genes of livers of wild type and IL-4/IL-13-/- two days after carbon tetrachloride treatment. Total RNA obtained from isolated livers from vehicle and carbon tetrachloride administered wild type and IL-4/IL-13-/- mice.

2013-06-05 | E-GEOD-45002 | biostudies-arrayexpress

Raw data for manuscript : "Serine synthesis via reversed SHMT2 activity drives glycine depletion and acetaminophen hepatotoxicity in MASLD"

Project description:Metabolic dysfunction-associated steatotic liver disease (MASLD) affects one third of the global population. Understanding metabolic pathways involved can provide insights into disease progression and treatment. Untargeted metabolomics of livers from mice with early-stage steatosis uncovered decreased methylated metabolites, suggesting altered one-carbon metabolism. The levels of glycine, a central component of one-carbon metabolism, were lower in mice with hepatic steatosis, consistent with clinical evidence. Stable-isotope tracing demonstrated that increased serine synthesis from glycine via reverse serine hydroxymethyltransferase (SHMT) is the underlying cause for decreased glycine in steatotic livers. Consequently, limited glycine availability in steatotic livers impaired glutathione synthesis under acetaminophen-induced oxidative stress, enhancing acute hepatotoxicity. Glycine supplementation or hepatocyte-specific ablation of the mitochondrial SHMT2 isoform in mice with hepatic steatosis mitigated acetaminophen-induced hepatotoxicity by supporting de novo glutathione synthesis. Thus, early metabolic changes in MASLD that limit glycine availability sensitize mice to xenobiotics even at the reversible stage of this disease.

2023-12-12 | MSV000093653 | MassIVE

Genome-wide analysis of gene expression of livers of wild type and IL-4/IL-13-/- mice after carbon tetrachloride-induced injury

Project description:Global analysis of differentially expressed genes of livers of wild type and IL-4/IL-13-/- two days after carbon tetrachloride treatment.

2013-06-05 | GSE45002 | GEO

Gene expression profiles of rat liver tissues after carbon tetrachloride administration

Project description:Liver cirrhosis (LC) is pathologically characterized with abnormality and necrosis of hepatic cells, proliferation of fibrous tissue, nodular regeneration and pseudolobule formation. We used Rat Genome 230 2.0 microarray to further highlight the rat liver tissues after carbon tetrachloride administration

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Gene expression profiles of rat liver tissues after carbon tetrachloride treatment

Project description:Acute hepatic failure (AHF) usually occurs due to the rapid necrosis of liver cells or serious liver injury induced by a variety of pathogenic factors. We used Rat Genome 230 2.0 microarray to further highlight the rat liver tissues after carbon tetrachloride treatment.

2015-09-29 | GSE73494 | GEO

Next Generation Sequencing (NGS) Facilitates Quantitative Analysis of Differentially Expressed Genes in Liver Regeneration After Combined Treatment With Ethanol And Carbon Tetrachloride

Project description:Purpose: The goals of this study are to use NGS-derived liver transcriptome profiling (RNA-seq) and identify differentially expressed genes in regenerating livers that were treated with ethanol and carbon tetrachloride. Methods: Liver mRNA profiles were generated from ethanol/CCl4-treated floxed homozytoes and Ctgf conditional knockout mice by deep sequencing, in duplicate, using Illumina GAIIx. qRT–PCR validation was performed using SYBR Green assay. Results: Ctgf deficiency was associated with 220 downregulated genes and 29 upregulated genes whereas Yap1 null livers had 351 downregulated genes and 287 upregulated genes after ethanol/CCl4 induced liver damage Conclusions: This study provides detailed analysis of liver transcriptomes in absence of Ctgf or Yap1 genes during ethanol/CCl4-induced injury, with biologic replicates, generated by RNA-seq technology.

2020-12-03 | GSE123309 | GEO

Gene expression changes of carbon tetrachloride-induced in renal cortex of rats

Project description:This study is to develop a short term and highly accurate prediction method of renal carcinogenicity based on gene expression profile of rats administrated by carcinogens. We conducted 28 days-repeated dose experiments in male SD rats with carbon tetrachloride, and the gene expression profiles of renal cortex were analyzed using custom microarrays.

2016-09-27 | GSE87249 | GEO

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