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Profiles of metabolites and gene expression in rats with chemically induced hepatic necrosis
- Publication Year :
- 2005
-
Abstract
- This study investigated whether integrated analysis of transcriptomics and metabolomics data increased the sensitivity of detection and provided new insight in the mechanisms of hepatotoxicity. Metabolite levels in plasma or urine were analyzed in relation to changes in hepatic gene expression in rats that received bromobenzene to induce acute hepatic centrilobular necrosis. Bromobenzene-induced lesions were only observed after treatment with the highest of 3 dose levels. Multivariate statistical analysis showed that metabolite profiles of blood plasma were largely different from controls when the rats were treated with bromobenzene, also at doses that did not elicit histopathological changes. Changes in levels of genes and metabolites were related to the degree of necrosis, providing putative novel markers of hepatotoxicity. Levels of endogenous metabolites like alanine, lactate, tyrosine and dimethylglycine differed in plasma from treated and control rats. The metabolite profiles of urine were found to be reflective of the exposure levels. This integrated analysis of hepatic transcriptomics and plasma metabolomics was able to more sensitively detect changes related to hepatotoxicity and discover novel markers. The relation between gene expression and metabolite levels was explored and additional insight in the role of various biological pathways in bromobenzene-induced hepatic necrosis was obtained, including the involvement of apoptosis and changes in glycolysis and amino acid metabolism. The complete Table 2 is available as a supplemental file online at http://taylorandfrancis.metapress.com/openurlasp?genre=journal&issn=0192-6233. To access the file, click on the issue link for 33(4), then select this article. A download option appears at the bottom of this abstract. In order to access the full article online, you must either have an individual subscription or a member subscription accessed through www.toxpath.org. Copyright © by the Society of Toxicologic Pathology.
- Subjects :
- Male
cycline
protein p53
Wistar
phosphatidylcholine sterol acyltransferase
blood level
Hepatitis
transcriptomics
dimethylglycine
orosomucoid
dose response
Centrilobular necrosis
tissue inhibitor of metalloproteinase 1
rat
Amino Acids
Principal Component Analysis
creatinine
apoptosis
article
peroxiredoxin
glycolysis
Toxicogenomics
liver toxicity
metabolomics
beta actin
priority journal
Liver
alanine
Drug
nucleophosmin
taurine
Transcription
protein bcl 2
Physiological Sciences
casein kinase II
amino acid metabolism
gene sequence
urine level
glyceraldehyde 3 phosphate dehydrogenase
Dose-Response Relationship
Necrosis
asialoglycoprotein receptor
Metabolite profiling
Genetic
unindexed drug
liver necrosis
Animals
bromobenzene
controlled study
cyclin G1
gene
Biology
phospholipid
nuclear magnetic resonance spectroscopy
methionine
nonhuman
protein p21
animal model
Gene Expression Profiling
Hepatotoxicity
ferritin
lactic acid
DNA microarray
nucleotide sequence
Toxic
Rats
fructose bisphosphate aldolase
phosphoglycerate mutase
creatine
tubulin
gene expression
fibrinogen
tyrosine
Bromobenzenes
Subjects
Details
- Language :
- English
- ISSN :
- 01926233
- Database :
- OpenAIRE
- Accession number :
- edsair.dris...00893..809269aa56d89aaa390221daa4ff3a64