Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats
The 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.
Acute 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.
The 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.
Colonic 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.
- Elson CO, Sartor RB, Targan SR, Sandborn WJ: Challenges in IBD research: Updating the scientific agendas. Inflamm Bowel Dis 2003, 9:137–153. CrossRef
- Plevy S, Mayer L: Meeting summary: Signal transduction pathways in immune and inflammatory cells. November 30−December 3, 2000, Amelia Island, Florida, U.S.A. Inflamm Bowel Dis 2003, 9:28–33. CrossRef
- Sawano M, Shimouchi A: A tracer analysis study on the redistribution and oxidization of endogenous carbon monoxide in the human body. J Clin Biochem Nutr 2010, 47:107–110. CrossRef
- Yamamoto T, Takano N, Ishiwata K, Suematsu M: Carbon monoxide stimulates global protein methylation via its inhibitory action on cystathionine beta-synthase. J Clin Biochem Nutr 2011, 48:96–100. CrossRef
- Naito Y, Takagi T, Uchiyama K, Yoshikawa T: Heme oxygenase-1: a novel therapeutic target for gastrointestinal diseases. J Clin Biochem Nutr 2011, 48:126–133. CrossRef
- Kajimura M, Fukuda R, Bateman RM, Yamamoto T, Suematsu M: Interactions of multiple gas-transducing systems: hallmarks and uncertainties of CO, NO, and H2S gas biology. Antioxid Redox Signal 2010, 13:157–192. CrossRef
- Takano N, Yamamoto T, Adachi T, Suematsu M: Assessing a shift of glucose biotransformation by lc-ms/ms-based metabolome analysis in carbon monoxide-exposed cells. Adv Exp Med Biol 2010, 662:101–107. CrossRef
- Kaizu T, Nakao A, Tsung A, Toyokawa H, Sahai R, Geller DA, Murase N: Carbon monoxide inhalation ameliorates cold ischemia/reperfusion injury after rat liver transplantation. Surgery 2005, 138:229–235. CrossRef
- Nakao A, Kimizuka K, Stolz DB, Neto JS, Kaizu T, Choi AM, Uchiyama T, Zuckerbraun BS, Nalesnik MA, Otterbein LE, Murase N: Carbon monoxide inhalation protects rat intestinal grafts from ischemia/reperfusion injury. Am J Pathol 2003, 163:1587–1598. CrossRef
- Nakao A, Toyokawa H, Abe M, Kiyomoto T, Nakahira K, Choi AM, Nalesnik MA, Thomson AW, Murase N: Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses. Transplantation 2006, 81:220–230. CrossRef
- Otterbein LE, Mantell LL, Choi AM: Carbon monoxide provides protection against hyperoxic lung injury. Am J Physiol 1999, 276:L688-L694.
- Otterbein LE, Bach FH, Alam J, Soares M, Tao Lu H, Wysk M, Davis RJ, Flavell RA, Choi AM: Carbon monoxide has anti-inflammatory effects involving the mitogen-activated protein kinase pathway. Nat Med 2000, 6:422–428. CrossRef
- Takagi T, Naito Y, Mizushima K, Akagiri S, Suzuki T, Hirata I, Omatsu T, Handa O, Kokura S, Ichikawa H, Yoshikawa T: Inhalation of carbon monoxide ameliorates TNBS-induced colitis in mice through the inhibition of TNF-alpha expression. Dig Dis Sci 2010, 55:2797–2804. CrossRef
- Takagi T, Naito Y, Uchiyama K, Suzuki T, Hirata I, Mizushima K, Tsuboi H, Hayashi N, Handa O, Ishikawa T, Yagi N, Kokura S, Ichikawa H, Yoshikawa T: Carbon monoxide liberated from carbon monoxide-releasing molecule exerts an anti-inflammatory effect on dextran sulfate sodium-induced colitis in mice. Dig Dis Sci 2011, 56:1663–1671. CrossRef
- Hegazi RA, Rao KN, Mayle A, Sepulveda AR, Otterbein LE, Plevy SE: Carbon monoxide ameliorates chronic murine colitis through a heme oxygenase 1-dependent pathway. J Exp Med 2005, 202:1703–1713. CrossRef
- Sheikh SZ, Hegazi RA, Kobayashi T, Onyiah JC, Russo SM, Matsuoka K, Sepulveda AR, Li F, Otterbein LE, Plevy SE: An anti-inflammatory role for carbon monoxide and heme oxygenase-1 in chronic th2-mediated murine colitis. J Immunol 2011, 186:5506–5513. CrossRef
- Uchida M, Mogami O: Milk whey culture with propionibacterium freudenreichii ET-3 is effective on the colitis induced by 2,4,6-trinitrobenzene sulfonic acid in rats. J Pharmacol Sci 2005, 99:329–334. CrossRef
- Takagi T, Yoshida N, Isozaki Y, Shimozawa M, Katada K, Manabe H, Hanada O, Kokura S, Ichikawa H, Naito Y, Okanoue T, Yoshikawa T: CV-11974, angiotensin II type I receptor antagonist, protects against ischemia-reperfusion injury of the small intestine in rats. Eur J Pharmacol 2006, 535:283–290. CrossRef
- Takaishi K, Ohtsuka T, Tsuneyoshi S, Maehara N, Harada M, Yoshida H, Watanabe K, Tsurufuji S: Inhibition of the production of rat cytokine-induced neutrophil chemoattractant (CINC)-1, a member of the interleukin-8 family, by adenovirus-mediated overexpression of IkappaBalpha. J Biochem 2000, 127:511–516. CrossRef
- Tomatsuri N, Yoshida N, Takagi T, Katada K, Isozaki Y, Imamoto E, Uchiyama K, Kokura S, Ichikawa H, Naito Y, Okanoue T, Yoshikawa T: Edaravone, a newly developed radical scavenger, protects against ischemia-reperfusion injury of the small intestine in rats. Int Journal Mol Med 2004, 13:105–109.
- Jick H, Walker AM: Cigarette smoking and ulcerative colitis. N Engl J Med 1983, 308:261–263. CrossRef
- Boyko EJ, Koepsell TD, Perera DR, Inui TS: Risk of ulcerative colitis among former and current cigarette smokers. N Engl J Med 1987, 316:707–710. CrossRef
- Lambert JD, Kennett MJ, Sang S, Reuhl KR, Ju J, Yang CS: Hepatotoxicity of high oral dose (−)-epigallocatechin-3-gallate in mice. Food Chem Toxicol 2010, 48:409–416. CrossRef
- Watanabe K, Koizumi F, Kurashige Y, Tsurufuji S, Nakagawa H: Rat CINC, a member of the interleukin-8 family, is a neutrophil-specific chemoattractant in vivo. Exp Mol Pathol 1991, 55:30–37. CrossRef
- Watanabe K, Konishi K, Fujioka M, Kinoshita S, Nakagawa H: The neutrophil chemoattractant produced by the rat kidney epithelioid cell line NRK-52E is a protein related to the KC/GRO protein. J Biol Chem 1989, 264:19559–19563.
- Zlotnik A, Yoshie O: Chemokines: A new classification system and their role in immunity. Immunity 2000, 12:121–127. CrossRef
- Megias J, Busserolles J, Alcaraz MJ: The carbon monoxide-releasing molecule corm-2 inhibits the inflammatory response induced by cytokines in caco-2 cells. Br J Pharmacol 2007, 150:977–986. CrossRef
- Allez M, Lemann M: Role of endoscopy in predicting the disease course in inflammatory bowel disease. World J Gastroenterol 2010, 16:2626–2632. CrossRef
- van Assche G, Vermeire S, Rutgeerts P: Mucosal healing and anti-TNFs in IBD. Curr Drug Targets 2010, 11:227–233. CrossRef
- Colombel JF, Sandborn WJ, Reinisch W, Mantzaris GJ, Kornbluth A, Rachmilewitz D, Lichtiger S, D'Haens G, Diamond RH, Broussard DL, Tang KL, van der Woude CJ, Rutgeerts P: Infliximab, azathioprine, or combination therapy for Crohn's disease. N Engl J Med 2010, 362:1383–1395. CrossRef
- Present DH: Toxic megacolon. Medical Clin North Am 1993, 77:1129–1148.
- Atkinson RJ, Save V, Hunter JO: Colonic ulceration after sodium phosphate bowel preparation. American J Gastroenterol 2005, 100:2603–2605. CrossRef
- Watts DA, Lessells AM, Penman ID, Ghosh S: Endoscopic and histologic features of sodium phosphate bowel preparation-induced colonic ulceration: case report and review. Gastrointest Endosc 2002, 55:584–587. CrossRef
- Driman DK, Preiksaitis HG: Colorectal inflammation and increased cell proliferation associated with oral sodium phosphate bowel preparation solution. Hum Pathol 1998, 29:972–978. CrossRef
- Menees S, Higgins P, Korsnes S, Elta G: Does colonoscopy cause increased ulcerative colitis symptoms? Inflamm Bowel Dis 2007, 13:12–18. CrossRef
- Colonic insufflation with carbon monoxide gas inhibits the development of intestinal inflammation in rats
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
Medical Gas Research
- Online Date
- September 2012
- Online ISSN
- BioMed Central
- Additional Links
- Carbon monoxide (CO)
- 2,4,6-Trinitrobenzene sulfonic acid (TNBS)-induced colitis
- Inflammatory bowel disease (IBD)
- Author Affiliations
- 1. Molecular Gastroenterology and Hepatology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto, 602-8566, Japan