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- Title
Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine.
- Authors
Katada, Kazuhiro; Bihari, Aurelia; Mizuguchi, Shinjiro; Yoshida, Norimasa; Yoshikawa, Toshikazu; Fraser, Douglas; Potter, Richard; Cepinskas, Gediminas
- Abstract
CORM-released CO has been shown to be beneficial in resolution of acute inflammation. The acute phase of intestinal ischemia-reperfusion (I/R) injury is characterized by oxidative stress-related inflammation and leukocyte recruitment. In this study, we assessed the effects and potential mechanisms of CORM-2-released CO in modulation of inflammatory response in the small intestine following I/R-challenge. To this end mice (C57Bl/6) small intestine were challenged with ischemia by occluding superior mesenteric artery (SMA) for 45 min. CORM-2 (8 mg/kg; i.v.) was administered immediately before SMA occlusion. Sham operated mice were injected with vehicle (0.25% DMSO). Inflammatory response in the small intestine (jejunum) was assessed 4 h following reperfusion by measuring tissue levels of TNF-α protein (ELISA), adhesion molecules E-selectin and ICAM-1 (Western blot), NF-κB activation (EMSA), along with PMN tissue accumulation (MPO assay) and leukocyte rolling/adhesion in the microcirculation of jejunum (intravital microscopy). The obtained results indicate that tissue levels of TNF-α, E-selectin and ICAM-1 protein expression, activation of NF-κB, and subsequent accumulation of PMN were elevated in I/R-challenged jejunum. The above changes were significantly attenuated in CORM-2-treated mice. Taken together these findings indicate that CORM-2-released CO confers anti-inflammatory effects by interfering with NF-κB activation and subsequent up-regulation of vascular pro-adhesive phenotype in I/R-challenged small intestine.
- Subjects
CARBON monoxide; ISCHEMIA; JEJUNUM; GENOTYPE-environment interaction; LEUCOCYTES; OXIDATIVE stress; SMALL intestine
- Publication
Inflammation, 2010, Vol 33, Issue 2, p92
- ISSN
0360-3997
- Publication type
Article
- DOI
10.1007/s10753-009-9162-y