title: Deleterious effects of indomethacin in the mid-gestation human intestine.
abstract: The use of the anti-inflammatory drug indomethacin (INDO) in preterm infants has been associated with an increased risk of developing enteropathies. In this study, we have investigated the direct impact of INDO on the human mid-gestation intestinal transcriptome using serum-free organ culture. After determining the optimal dose of 1 μM of INDO (90% inhibition of intestinal prostaglandin E2 production and range of circulating levels in treated preterm babies), global gene expression profiles were determined using Illumina bead chip microarrays in both small and large intestines after 48 h of INDO treatment. Using Ingenuity Pathway Analysis software, we identified critical metabolic pathways that were significantly altered by INDO in both intestinal segments including inflammation and also glycolysis, oxidative phosphorylation and free radical scavenging/oxidoreductase activity, which were confirmed by qPCR at the level of individual genes. Taken together, these data revealed that INDO directly exerts multiple detrimental effects on the immature human intestine.
authors.affiliation: Research Consortium on Child Intestinal Inflammation, Department of Anatomy and Cell Biology, Faculté de Médecine et des Sciences de la Santé, Université de Sherbrooke, Sherbrooke, QC, Canada.
authors.forename: Nancy
authors.initials: N
authors.lastname: Perron
authors.forename: Eric
authors.initials: E
authors.lastname: Tremblay
authors.forename: Emanuela
authors.initials: E
authors.lastname: Ferretti
authors.forename: Corentin
authors.initials: C
authors.lastname: Babakissa
authors.forename: Ernest G
authors.initials: EG
authors.lastname: Seidman
authors.forename: Emile
authors.initials: E
authors.lastname: Levy
authors.forename: Daniel
authors.initials: D
authors.lastname: Ménard
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Beaulieu
mesh_terms: D037881:Aborted Fetus / Q000378:metabolism / Q000473:pathology; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007213:Indomethacin / Q000008:administration & dosage*; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000503:physiopathology; D053858:Metabolic Networks and Pathways / Q000235:genetics*; D009924:Organ Culture Techniques; D011247:Pregnancy; D047928:Premature Birth / Q000188:drug therapy / Q000378:metabolism* / Q000503:physiopathology; D059467:Transcriptome / Q000187:drug effects* / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D007213:Indomethacin