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Title: Transcriptional analysis of organ-specific toxicity induced by a panPPAR agonist in mice: Identification of organ-specific toxicity biomarkers      
dateReleased:
02-19-2013
description:
In this study, we aim to identify candidate biomarkers which may be useful as surrogate indicators of toxicity for pre-clinical development of panPPAR-agonist drug candidates. Gene expression microarray, histopathology and clinical chemistry data were generated from liver, heart, kidney and skeletal muscles of three groups of mice administered with three different dosages of an experimental pan-peroxisome proliferator-activated receptor (pan-PPAR) agonist, PPM-201, for 14 days. The histopathology and clinical chemistry data were compared with the gene expression analysis and candidate biomarker genes were identified. Nine wild type mice (strain: C57BL/6J) were randomly divided into three groups - Group-I, II and III. PPM-201 in the vehicle base was administered daily for 14 days at 6 mg/kg body weight dose rate to each mouse in Group-II and at 20mg/kg body weight dose rate to each mouse in Group-III while the mice in Group-I received only the vehicle base. On 15th day, the mice were sacrificed to harvest blood, heart, skeletal muscle, liver and kidney tissues for clinical chemistry, microarray and histopathology analysis. In the clinical chemistry analysis, alanine aminotransferase (ALT, U/L), aspartate aminotransferase (AST, U/L), creatinine kinase (CK, U/L), blood urea nitrogen (BUN, mmol/L), creatinine (umol/L) and lactate dehydrogenase (LDH, U/L) were measured from the blood of each mouse. Two sections of liver, two sections of kidney, one or two sections of skeletal muscle, and one section of heart were prepared from each mouse, stained with hematoxylin and eosin (H&E), and examined by a veterinary pathologist. RNA was extracted and processed as per the established protocol from heart, skeletal muscle, liver and kidney tissue samples of all the 9 mice for profiling with Affymetrix Mouse Genome 430 2.0 Array and in total 36 chips were prepared. Using various quality control measures, the data was analysed for its quality. As it was found to be good in quality, the data from all the 36 chips were used for further analysis. The results from histopathology and clinical chemistry analysis were compared with the gene expression to determine if the dosages selected for the study were associated with findings in target organs.
privacy:
not applicable
aggregation:
instance of dataset
ID:
E-GEOD-31561
refinement:
raw
alternateIdentifiers:
31561
keywords:
functional genomics
dateModified:
06-02-2014
availability:
available
types:
gene expression
name:
Mus musculus
ID:
A-AFFY-45
name:
Affymetrix GeneChip Mouse Genome 430 2.0 [Mouse430_2]
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-31561/E-GEOD-31561.raw.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ebi.ac.uk/arrayexpress/files/E-GEOD-31561/E-GEOD-31561.processed.1.zip
storedIn:
ArrayExpress
qualifier:
gzip compressed
format:
TXT
accessType:
download
authentication:
none
authorization:
none
accessURL: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE31561
storedIn:
Gene Expression Omnibus
qualifier:
not compressed
format:
HTML
accessType:
landing page
primary:
true
authentication:
none
authorization:
none
abbreviation:
EBI
homePage: http://www.ebi.ac.uk/
ID:
SCR:004727
name:
European Bioinformatics Institute
homePage: https://www.ebi.ac.uk/arrayexpress/
ID:
SCR:002964
name:
ArrayExpress
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