Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Drug-induced hepatotoxicity screening in primary mouse hepatocytes, an Omics approach.

ABSTRACT: Drug-induced hepatotoxicity is a leading cause of attrition of candidate drugs in drug development. Therefore new screening methods are necessary which predict these hazards more accurate and earlier in the drug development process. Of all in vitro hepatotoxicity models, primary human hepatocytes are considered as 'the gold standard'. However, the use of these hepatocytes is hindered by their scarcity and major inter-individual variation. These limitations may be overcome with use of primary mouse hepatocytes. Within this context changes in protein expressions in primary mouse hepatocytes, after exposure to cyclosporin A were studied using differential gel electrophoresis. Thereafter, the mRNA expression levels of these deregulated proteins from cyclosporin A-treated cells were analyzed. Cyclosporin A induced ER stress and altered the ER-Golgi transport, which may alter vesicle mediated transport and protein secretion. Moreover are the differentially expressed proteins observed upon challenge by cyclosporin A, associated with cholestatic mechanisms.

ORGANISM(S): Mus musculus

PROVIDER: GSE33742 | GEO | 2013/04/01

SECONDARY ACCESSION(S): PRJNA148421

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Drug-induced hepatotoxicity screening in primary mouse hepatocytes, an Omics approach.

Project description:Drug-induced hepatotoxicity is a leading cause of attrition of candidate drugs in drug development. Therefore new screening methods are necessary which predict these hazards more accurate and earlier in the drug development process. Of all in vitro hepatotoxicity models, primary human hepatocytes are considered as 'the gold standard'. However, the use of these hepatocytes is hindered by their scarcity and major inter-individual variation. These limitations may be overcome with use of primary mouse hepatocytes. Within this context changes in protein expressions in primary mouse hepatocytes, after exposure to cyclosporin A were studied using differential gel electrophoresis. Thereafter, the mRNA expression levels of these deregulated proteins from cyclosporin A-treated cells were analyzed. Cyclosporin A induced ER stress and altered the ER-Golgi transport, which may alter vesicle mediated transport and protein secretion. Moreover are the differentially expressed proteins observed upon challenge by cyclosporin A, associated with cholestatic mechanisms. For each biological experiment, one hybridization was conducted and one sample per array. In total, 6 arrays were used for 2 different conditions (Csa or control at 48 hours).

2013-04-01 | E-GEOD-33742 | biostudies-arrayexpress

PHH treated with IBU, CPZ, CsA, AMI

Project description:Drug-induced hepatotoxicity is still one of the main reasons for drug attrition; therefore, there is an urgent need for more predictive models to identify the toxic potential of new drug candidates. Here, transcriptomic data from short- and long-term cultured primary human hepatocytes exposed to four pharmaceuticals, namely ibuprofen, chlorpromazine, cyclosporine A and amiodarone was analysed.

2014-09-01 | E-MTAB-2473 | 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

PHH Chlorpromazine

Project description:Drug induced liver injury (DILI) is still a major reason for drug attrition during clinical trials and market-withdrawal of already approved drugs. DILI is difficult to predict in animal models, hence more suitable screening methods are needed to predict adverse effects in human. Here, transcriptomic data from short- and long-term cultured primary human hepatocytes exposed to the human hepatotoxin Chlorpromazine was analysed.

2013-08-05 | E-MTAB-1747 | biostudies-arrayexpress

Mus musculus

Project description:Drug-induced hepatotoxicity screening in primary mouse hepatocytes, an Omics approach.

| PRJNA148421 | ENA

RNA-sequencing with human liver organoids derived from human induced pluripotent stem cells

Project description:We established a human liver organoid (HLO) based screening model for analyzing DILI pathology at organoid resolution. HLO contains polarized immature hepatocytes with bile canaliculi-like architecture, establishing the unidirectional bile acid transport pathway. Single cell RNAseq profiling identified diverse and zonal hepatocytic populations that in part emulate primary adult hepatocytes. By developing a 384 well based high-speed live imaging platform, we successfully developed a Liver organoid-based Toxicity screen (LoT) with multiplexed readouts measuring viability, cholestatic and/or mitochondrial toxicity. We functionally validated LoT with 238 marketed drugs at 4 different concentrations. LoT positively predicts genomic predisposition (CYP2C9*2) for Bosentan-induced cholestasis. Thus, LoT is a high-fidelity model for drug safety with a cost-effective platform, facilitating compound optimization, mechanistic study, and precision medicine as well as drug screening applications.

2020-10-18 | GSE141183 | GEO

Expression Profiles of Primary Mouse Hepatocytes treated with Cyclosporin A and solvent control [RNA]

Project description:The transcriptomics changes induced in Primary Mouse Hepatocytes by Cyclosporin A after treatment for 24h and 48h The study investigated differential gene expression in Primary Mouse Hepatocytes mRNA following 24 and 48 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/solvent. In total 24 arrays .

2014-07-24 | E-GEOD-55881 | biostudies-arrayexpress

Expression Profiles of Primary Mouse Hepatocytes treated with Cyclosporin A and solvent control [miRNA]

Project description:The microRNA changes induced in Primary Mouse Hepatocytes of C57Bl6-mice by Cyclosporin A after treatment for 24h and 48h The study investigated differential microRNA expression in Primary Mouse Hepatocytes following 24 and 48 hours of exposure to Cyclosporin A and solvent. Three biological replicates per compound/six per solvent. In total 24 arrays .

2014-07-24 | E-GEOD-55880 | biostudies-arrayexpress

Expression data for iPSC-derived hepatocyte-like cells (HLCs) treated with 100 µM pazopanib for 24 hours

Project description:Pazopanib is a drug with idiosyncratic hepatotoxicity risk. Analysis of gene expression changes after exposing hepatocytes can indicate effects on specific biological pathways and potential mechanisms of hepatotoxicity. HLCs derived from patient-specific iPSCs were treated with pazopanib to identify both drug-related global effects and patient-specific effects

2016-09-30 | GSE75888 | GEO

Rutin attenuates ensartinib-induced hepatotoxicity by non-transcriptional regulation of TXNIP

Project description:Ensartinib, an approved ALK inhibitor, is used as the first-line therapy for advanced ALK-positive non-small cell lung cancer in China. Ensartinib shows superior efficacy to crizotinib in both systemic and intracranial disease and is prepared to be reviewed overseas. In future, more patients would benefit from it based on its efficacy. However, a high incidence of hepatotoxicity has been observed in clinic, which often demands dose reduction or discontinuation of the drug, hampering its overall efficacy. Hence, it is inevitably valuable to study the mechanism which would be benefit to overcome the ensartinib-induced hepatotoxicity. In addition, based on the toxicity model, it is well established to understand the process of drug-induced liver injury and hepatic function-related molecules. Our findings discovered the level and location of TXNIP in liver homeostasis regulatory, clarified the molecular mechanism for ensartinib-induced hepatotoxicity and identified rutin as a potential strategy for the first time. We find a novel mode of rutin in intervening ROS production and apoptosis by binding TXNIP. Our study is of great significance to the basic theories and clinical practice. And this work is of broad interest to the readers from drug discovery, hepatologists in this filed and biologists in redox homeostasis.

2024-05-29 | GSE249370 | GEO

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data