Abstract
BackgroundThe pathogenesis of inflammatory bowel disease (IBD) is complex, and an effective therapeutic strategy has yet to be established. Recently, carbon monoxide (CO) has been reported to be capable of reducing inflammation by multiple mechanisms. In this study, we evaluated the role of colonic CO insufflation in acute colitis induced by trinitrobenzene sulfonic acid (TNBS) in rats.MethodsAcute colitis was induced with TNBS in male Wistar rats. Following TNBS administration, the animals were treated daily with 200 ppm of intrarectal CO gas. The distal colon was removed to evaluate various parameters of inflammation, including thiobarbituric acid (TBA)-reactive substances, tissue-associated myeloperoxidase (MPO) activity, and the expression of cytokine-induced neutrophil chemoattractant (CINC)-1 in colonic mucosa 7 days after TNBS administration.ResultsThe administration of TNBS induced ulceration with surrounding edematous swelling in the colon. In rats treated with CO gas, the colonic ulcer area was smaller than that of air-treated rats 7 days after TNBS administration. The wet colon weight was significantly increased in the TNBS-induced colitis group, which was markedly abrogated by colonic insufflation with CO gas. The increase of MPO activity, TBA-reactive substances, and CINC-1 expression in colonic mucosa were also significantly inhibited by colonic insufflation with CO gas.ConclusionsColonic insufflation with CO gas significantly ameliorated TNBS-induced colitis in rats. Clinical application of CO gas to improve colonic inflammatory conditions such as IBD might be useful.
Highlights
The pathogenesis of inflammatory bowel disease (IBD) is complex, and an effective therapeutic strategy has yet to be established
In the present study, we demonstrated that insufflation of carbon monoxide (CO) gas into the colonic lumen decreased colonic mucosal damage and inflammation induced by trinitrobenzene sulfonic acid (TNBS)
In previous study using murine colonic epithelial cells, we demonstrated that CO inhibited the production of keratinocyte chemoattractant (KC), which has represented a closely related chemokine involved in neutrophil recruitment [26] and been regarded as a functional homologue of IL-8, through the inhibition of NF-κB activation [14]
Summary
The pathogenesis of inflammatory bowel disease (IBD) is complex, and an effective therapeutic strategy has yet to be established. The anti-inflammatory effect of CO has been reported in various disease states and experimental models, including ischemia-reperfusion injury [8,9], organ transplantation [10], hyperoxia [11], and lipopolysaccharide (LPS)-induced sepsis [12] In these conditions, CO-mediated protection is associated with suppression of the inflammatory cytokine response. CO inhalation suppressed inflammation in a genetically induced mouse colitis model, in interleukin (IL)-10-deficient mice [15], and in T cell receptor (TCR)α-deficient mice [16]. Based on these reports, CO administration might represent a potential therapeutic strategy for IBD
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.
