Document Detail


Comprehensive analysis of differential gene expression profiles on diclofenac-induced acute mouse liver injury and recovery.
MedLine Citation:
PMID:  16859844     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microarray analysis of RNA from diclofenac-administered mouse livers was performed to establish a global gene expression profile during injury and recovery stages at two different doses. A single dose of diclofenac at 9.5 mg/kg or 0.95 mg/kg body weight was given orally, and the liver samples were obtained after 6, 24, and 72 h. Histopathologic studies enabled the classification of the diclofenac effect into injury (6, 24 h) and recovery (72 h) stages. By using the Applied Biosystems Mouse Genome Survey Microarray, a total of 7370 out of 33,315 (22.1%) genes were found to be statistically reliable at p<0.05 by two-way ANOVA, and 602 (1.8%) probes at false discovery rate <5% by Significance Analysis of Microarray. Among the statistically reliable clones by both analytical methods, 49 genes were differentially expressed with more than a 1.625-fold difference (which equals 0.7 in log(2) scale) at one or more treatment conditions. Forty genes and two genes were identified as injury- and recovery-specific genes, respectively, showing that most of the transcriptomic changes were seen during the injury stage. Furthermore, multiple genes involved in oxidative stress, eicosanoid synthesis, apoptosis, and ATP synthesis showed variable transcript levels upon acute diclofenac administration.
Authors:
Heekyoung Chung; Hyun-Jun Kim; Ki-Seok Jang; Mingoo Kim; Jungeun Yang; Ju Han Kim; Yong-Sung Lee; Gu Kong
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Publication Detail:
Type:  Journal Article     Date:  2006-06-12
Journal Detail:
Title:  Toxicology letters     Volume:  166     ISSN:  0378-4274     ISO Abbreviation:  Toxicol. Lett.     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-08-28     Completed Date:  2006-10-13     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7709027     Medline TA:  Toxicol Lett     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  77-87     Citation Subset:  IM    
Affiliation:
Department of Pathology, College of Medicine, Hanyang University, Seongdong-gu, Seoul 133-791, Republic of Korea.
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MeSH Terms
Descriptor/Qualifier:
Animals
Anti-Inflammatory Agents, Non-Steroidal / adverse effects*
Diclofenac / adverse effects*
Drug-Induced Liver Injury / etiology*,  genetics,  pathology
Gene Expression / drug effects*
Gene Expression Profiling
Liver / drug effects*,  metabolism,  pathology
Liver Regeneration / genetics*
Male
Mice
Mice, Inbred ICR
Oligonucleotide Array Sequence Analysis
Oxidative Stress / drug effects,  genetics
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 15307-86-5/Diclofenac

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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