Comprehensive analysis of differential gene expression profiles on diclofenac-induced acute mouse liver injury and recovery.
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.
Chung
Heekyoung
H
Department of Pathology, College of Medicine, Hanyang University, Seongdong-gu, Seoul 133-791, Republic of Korea.
Kim
Hyun-Jun
HJ
Jang
Ki-Seok
KS
Kim
Mingoo
M
Yang
Jungeun
J
Kim
Ju Han
JH
Lee
Yong-Sung
YS
Kong
Gu
G
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects*; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology* / Q000235:genetics / Q000473:pathology; D004008:Diclofenac / Q000009:adverse effects*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D008115:Liver Regeneration / Q000235:genetics*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac