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Hepatic Gene Expression Profiling and Lipid Homeostasis in Mice Exposed to Steatogenic Drug, Tetracycline
- Source :
- Toxicological Sciences. 94:206-216
- Publication Year :
- 2006
- Publisher :
- Oxford University Press (OUP), 2006.
-
Abstract
- Tetracycline is one of a group of drugs known to induce microvesicular steatosis. In the present study, we investigated the effects of tetracycline on gene expression in mouse liver, using Applied Biosystems Mouse Genome Survey Microarrays. A single oral dose of 0.1 or 1 g/kg tetracycline was administered to male ICR mice, and liver samples were obtained after 6, 24, or 72 h. Histopathological evaluation showed microvesicular steatosis in the high-dose group at 24 h. In total, 96 genes were identified as tetracycline responsive. Their level of expression differed significantly from controls (two-way analysis of variance; p0.05), after adjustment by the Benjamini-Hochberg multiple testing correction, and displayed a twofold or greater induction or repression. The largest groups of gene products affected by tetracycline exposure were those involved in signal transduction, nucleic acid metabolism, developmental processes, and protein metabolism. The expression of genes known to be involved in lipid metabolism was examined, using two-sample Student's t-test for each treatment group versus a corresponding control group. The overall net effects on expression of lipid metabolism genes indicated an increase in cholesterol and triglyceride biosynthesis and a decrease in beta-oxidation of fatty acids. Our data support a proposed mechanism for tetracycline-induced steatogenic hepatotoxicity that involves these processes. Moreover, we demonstrated global changes in hepatic gene expression following tetracycline exposure; many of these genes have the potential to be used as biomarkers of exposure to steatogenic hepatotoxic agents.
- Subjects :
- Male
medicine.medical_specialty
Time Factors
Microarray
Tetracycline
Microvesicular Steatosis
Protein metabolism
Administration, Oral
Biology
Toxicology
Mice
chemistry.chemical_compound
Internal medicine
Gene expression
medicine
Animals
Cluster Analysis
Homeostasis
Oligonucleotide Array Sequence Analysis
Protein Synthesis Inhibitors
Analysis of Variance
Mice, Inbred ICR
Dose-Response Relationship, Drug
Reverse Transcriptase Polymerase Chain Reaction
Gene Expression Profiling
Lipid metabolism
Lipid Metabolism
Molecular biology
Fatty Liver
Gene expression profiling
Endocrinology
Liver
chemistry
Toxicogenomics
Signal Transduction
medicine.drug
Subjects
Details
- ISSN :
- 10960929 and 10966080
- Volume :
- 94
- Database :
- OpenAIRE
- Journal :
- Toxicological Sciences
- Accession number :
- edsair.doi.dedup.....3c30a63757593e8b7504fd70cd75e9ef