Type

Journal Article

Authors

Carlos Medina
John F Gilmer
Samuel Kana Lis
Noreen Boyle
Neil Docherty
Maria T Pigott
Jun Wang
Shane O'Sullivan

Subjects

Pharmacology

Topics
gene expression drinking water anti inflammatory rats wistar matrix metalloproteinase 9 nitric oxide low density inflammatory bowel disease

Inhibition of matrix metalloproteinase-9 by a barbiturate-nitrate hybrid ameliorates dextran sulphate sodium-induced colitis: effect on inflammation-related genes. (2016)

Abstract Matrix metalloproteinase-9 (MMP-9) is up-regulated in ulcerative colitis and implicated in the pathology of the disease. In this study, we have examined the effects of a barbiturate-based MMP inhibitor incorporating a nitric oxide donor/mimetic group (dinitrate-barbiturate) on the intestinal injury induced by dextran sulphate sodium (DSS). In vivo experiments were carried out using male Wistar rats given 5% DSS ad libitum in drinking water. The dinitrate-barbiturate, non-nitrate equivalent, nitrate side chains alone or vehicle were administered rectally, twice daily. MMP-9 release was measured by gelatin zymography, and analysis of gene expression was carried out using RT-qPCR. TaqMan low density arrays were used to evaluate the expression of 91 inflammatory genes in the rat colon. The dinitrate-barbiturate inhibited the induction and activity of MMP-9 during DSS colitis in the rat. This occurred in association with significant reductions in the colitic response to DSS as assessed by an established clinical disease activity index and a pathological colitis grade score. The compound modified expression rates of numerous inflammation-related genes in the colon. This study demonstrated the efficacy of the dinitrate-barbiturate in DSS-induced colitis. Therefore, barbiturate-nitrate hybrids may be developed as a promising anti-inflammatory approach to the treatment of inflammatory bowel disease.
Collections Ireland -> Trinity College Dublin -> PubMed

Full list of authors on original publication

Carlos Medina, John F Gilmer, Samuel Kana Lis, Noreen Boyle, Neil Docherty, Maria T Pigott, Jun Wang, Shane O'Sullivan

Experts in our system

1
Carlos Medina
Trinity College Dublin
Total Publications: 23
 
2
John Gilmer
Trinity College Dublin
Total Publications: 28
 
3
Neil G Docherty
University College Dublin
Total Publications: 57
 
4
Jun Wang
Trinity College Dublin
Total Publications: 37
 
5
Shane P. O'Sullivan
University College Cork
Total Publications: 13