Poster: Comprehensive gene expression

Comprehensive gene expression analysis of mice liver treated with Diclofenac
AUTHOR(S): 

Eun-Hee Lee, Heeyoung Yang, Seokjoo Yoon / Korea Institute of Toxicology

PRESENTING AUTHOR: 

Seokjoo Yoon. Korea Institute of Toxicology

OpenTox Euro 2014 Poster: Comprehensive gene expression analysis of mice liver treated with Diclofenac

POSTER ABSTRACT / DETAILS:
As a nonsteroidal anti-inflammatory drug, diclofenac is used to treat pain and reduce inflammation associated with arthritis. It is known to be associated with idiosyncratic adverse drug reaction incidence. The cause of idiosyncratic liver injury remains vague and likely to interact with multifactor.

To better understand the hepatotoxic mechanism of diclofenac, we analyzed whole genome expression profiles in mouse liver administered diclofenac (30 mg/kg, i.p.) once per day for 1 day or 3 days. In total, 295 and 467 significantly regulated genes were selected, respectively, as defined by the Welch’s t-test (P < 0.05) and threshold of fold change ≥1.5 using the GenePlex analysis program. Notably, 29 genes were commonly regulated after single and repeated treatment.

The majors being closely associated with inflammatory, immune and acute phase responses. We analyzed bio-functions, canonical pathways and regulator effects prediction using the ingenuity pathway analysis software. The most distinguishable regulations in gene expression change were linked to inflammatory response, cellular movement, hematological system development/function and immune cell trafficking in both samples. Also, in the canonical pathways, acute phase response and interleukin-related signaling were significantly implicated in single and repeated treatment.

Among the upstream regulator, Stat3, transcriptional factor, was significantly influenced by diclofenac. And some of inflammatory protein was increased by diclofenac. In the results of the microarray analysis, the expression of genes associated with the inflammatory, acute phase, and immune responses was significantly influenced by diclofenac.