Abstract
Background: Oxidative stress plays a role in the pathogenesis of inflammatory bowel disease (IBD). The Paraoxonase (PON) genes, expressed in the human intestine, are thought to prevent oxidative stress and modulate inflammation. We investigated the effect of IBD and steroids on PON gene. We hypothesized that PON gene expression is decreased in IBD patients and that steroid treatment would return it to normal.Methods: Pediatric patients diagnosed with IBD, were enrolled and matched to control subjects. For in vitro studies, human epithelial colorectal adenocarcinoma (Caco-2) cells were treated with hydrogen peroxide (H2O2) and dexamethasone. PON genes expression was evaluated by quantitative real-time PCR for both the biopsies and the Caco-2 cells.Results: PON gene expression was decreased in intestinal biopsies from medication naive IBD patients when compared to controls (p<0.05). Biopsies from IBD patients on steroids exhibited up regulation of PON gene expression (p<0.05). Caco-2 cells treated with H2O2 had decreased PON gene expression compared to controls (p<0.05). Dexamethasone increased PON gene expression in Caco-2 cells (p<0.05).Conclusion: Our data suggests that decreased PON expression in IBD patients is a consequence of oxidative stress which plays a role in the pathogenesis of IBD. Further, steroids counteract the effect of oxidative stress by up regulating PON gene expression. PON genes may be targets for the management of intestinal diseases like IBD.
Highlights
Inflammatory Bowel Disease (IBD) is a chronic relapsing inflammatory condition that affects the gastrointestinal tract
Human study A total of 35 patients were included in the study, 10 medication naïve Crohn’s disease (CD), 10 medication naïve ulcerative colitis (UC), 5 inflammatory bowel disease (IBD) patients on steroids (3 CD, 2 UC) and 10 control subjects
In a study of adult patients with IBD Boehm et al found that PON1 protein activity was decreased in IBD patients when compared to controls [21]
Summary
Inflammatory Bowel Disease (IBD) is a chronic relapsing inflammatory condition that affects the gastrointestinal tract. It is comprised of two major phenotypes, Crohn’s disease (CD) and ulcerative colitis (UC) [1]. Oxidative stress arises when there is marked imbalance between the production of reactive oxygen species (ROS) and their removal by antioxidants. Both animal and human studies link oxidative stress and IBD [3]. The most striking evidence in animal studies comes from genetic knockout mice lacking glutathione peroxidase (GPX). We hypothesized that PON gene expression is decreased in IBD patients and that steroid treatment would return it to normal
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
