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NSAIDs Cause Significant Changes in Gene Expression in Small Intestinal Epithelial Cells
Author(s) -
Silver Kris,
Lillich James
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.619.1
Subject(s) - toxicity , gene expression , pharmacology , duodenum , gastrointestinal tract , in vivo , caco 2 , medicine , gene , in vitro , biology , biochemistry , microbiology and biotechnology
Non‐steroidal anti‐inflammatory drugs (NSAIDs) are among the most widely used drugs for the amelioration of pain and inflammation. Unfortunately, NSAIDs are commonly associated with a wide range of toxic side effects, particularly in the gastrointestinal tract (GI). Though indiscriminant inhibition of COX enzymes has been suggested as a cause of adverse GI side‐effects, mounting evidence indicates that COX inhibition and loss of prostaglandin production do not entirely explain NSAID‐induced GI effects, and that other mechanisms also contribute to NSAID toxicity. Currently lacking from the body of NSAID activity/toxicity data is a genomic level examination of the effects of NSAIDs in vivo on gene expression in intestinal epithelial cells. Therefore, the current project was undertaken to examine the effects of oral NSAID treatment on gene expression in rat duodenal mucosa. Rats were treated with control, indomethacin (non‐specific), or NS‐398 (COX‐2 specific) for 72 h. Rats were then euthanized and mucosal scrapings were collected from rat duodenum. RNA was isolated then subjected to Illumina sequencing and comparisons of gene expression in duodenal mucosa revealed 698 or 17 genes that had significantly altered expression following oral treatment with indomethacin or NS‐398, respectively. A total of eight genes (one up and seven down) were affected by both indomethacin and NS‐398 treatment, including stomatin (up), amylase 2A3, carboxyl ester lipase, RGD1561381, Tmem238, ENSRNOG15847, Lsm5, and Tceal8. Our results provide new insight into the mechanisms involved in NSAID‐induced GI toxicity and provide a basis for future experiments aimed at understanding the complex interactions between NSAIDs, intestinal epithelia, and the intestinal lumen.