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Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine

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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.

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Acknowledgements

This study was supported by the research grants from the Heart and Stroke Foundation of Ontario; HSFO-NA6171 and Lawson Health Research Institute Internal Research Fund; IRF -025-09 (G. Cepinskas) and Canadian Institutes for Health Research; MOP-68848 (R. F. Potter). Dr. Shinjiro Mizuguchi (co-author) is a recipient of the Government of Canada Post-Doctoral Research Fellowship.

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Authors and Affiliations

  1. Centre for Critical Illness Research, Lawson Health Research Institute, 800 Commissioners Rd., London, ON, N6A4G5, Canada

    Kazuhiro Katada, Aurelia Bihari, Shinjiro Mizuguchi, Douglas D. Fraser, Richard F. Potter & Gediminas Cepinskas

  2. Department of Surgery, University of Western Ontario, London, ON, Canada

    Richard F. Potter

  3. Dept. Inflammation and Immunology, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, Kyoto, Japan

    Norimasa Yoshida & Toshikazu Yoshikawa

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  1. Kazuhiro Katada
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  8. Gediminas Cepinskas
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Katada, K., Bihari, A., Mizuguchi, S. et al. Carbon Monoxide Liberated from CO-Releasing Molecule (CORM-2) Attenuates Ischemia/Reperfusion (I/R)-Induced Inflammation in the Small Intestine. Inflammation 33, 92–100 (2010). https://doi.org/10.1007/s10753-009-9162-y

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