An integrated functional genomic study of acute phenobarbital exposure in the rat View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2010-12

AUTHORS

Claire L Waterman, Richard A Currie, Lisa A Cottrell, Jacky Dow, Jayne Wright, Catherine J Waterfield, Julian L Griffin

ABSTRACT

BACKGROUND: Non-genotoxic carcinogens are notoriously difficult to identify as they do not damage DNA directly and have diverse modes of action, necessitating long term in vivo studies. The early effects of the classic rodent non-genotoxic hepatocarcinogen phenobarbital have been investigated in the Fisher rat using a combination of metabolomics and transcriptomics, to investige early stage mechanistic changes that are predictive of longer term pathology. RESULTS: Liver and blood plasma were profiled across 14 days, and multivariate statistics used to identify perturbed pathways. Both metabolomics and transcriptomics detected changes in the liver which were dose dependent, even after one day of exposure. Integration of the two datasets associated perturbations with specific pathways. Hepatic glycogen was decreased due to a decrease in synthesis, and plasma triglycerides were decreased due to an increase in fatty acid uptake by the liver. Hepatic succinate was increased and this was associated with increased heme biosynthesis. Glutathione synthesis was also increased, presumably in response to oxidative stress. Liquid Chromatography Mass Spectrometry demonstrated a remodeling of lipid species, possibly resulting from proliferation of the smooth endoplasmic reticulum. CONCLUSIONS: The data fusion of metabolomic and transcriptomic changes proved to be a highly sensitive approach for monitoring early stage changes in altered hepatic metabolism, oxidative stress and cytochrome P450 induction simultaneously. This approach is particularly useful in interpreting changes in metabolites such as succinate which are hubs of metabolism. More... »

PAGES

9

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/1471-2164-11-9

DOI

http://dx.doi.org/10.1186/1471-2164-11-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1039819082

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/20053287


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Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-11-9'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-11-9'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-11-9'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1186/1471-2164-11-9'


 

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