Published in:
01-04-2010
Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine
Authors:
Kazuhiro Katada, Aurelia Bihari, Shinjiro Mizuguchi, Norimasa Yoshida, Toshikazu Yoshikawa, Douglas D. Fraser, Richard F. Potter, Gediminas Cepinskas
Published in:
Inflammation
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Issue 2/2010
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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.