CO liberated from CORM-2 modulates the inflammatory response in the liver of thermally injured mice

Abstract

CORM-released CO modulates liver inflammation and significantly protects liver injury in burn mice by inhibiting the expression of iNOS and NO production, down-regulating the expression of pro-inflammatory mediators (TNF-alpha, IL-1beta).

Exogenous carbon monoxide suppresses Escherichia coli vitality and improves survival in an Escherichia coli-induced murine sepsis model

“…In the present study, we found that MPO activity in liver and lung tissues was signifi-cantly elevated after bacterial infection and this effect was significantly attenuated after in vivo administration of CORM-2 but not iCORM-2. In accordance with previously reports [15,17] , this finding indicated that treatment with CORM-2 effectively prevented PMN chemotaxis and infiltration of liver and lung tissues after bacterial infection, consequently decreasing the production of oxidants, and reducing oxidant-mediated injury and inflammatory response in these tissues.…”

“…Recently, transitional metal carbonyls have been identified as potential CO-releasing molecules (CORMs) with the potential to deliver CO to tissues and organs as a therapeutic agent [12,13] . We have reported that CORM-2 attenuated leukocyte sequestration in some vital organs and the small intestine in burned and cecal ligation and puncture (CLP)-challenged mouse models of sepsis through interfering with nuclear factor-κB (NF-κB) activation and intercellular adhesion molecule-1 (ICAM-1) protein expression and suppressing the endothelial cell proadhesive phenotype [14][15][16][17] . In addition, our earlier studies also showed that CORM-2 inhibits the activity and virulence of E coli in vitro.…”

Bench-to-bedside review: Carbon monoxide – from mitochondrial poisoning to therapeutic use

“…Downregulation of MEK/ERK1/2 seems to play a role in mediating the protective effects while the NF-κB signaling pathway does not seem to be affected [94]. CO-RM-liberated CO attenuates liver injury in burn mice by mechanisms involving downregulation of pro-inflammatory mediators and suppression of the pro-adhesive phenotype of endothelial cells [95,96]. …”

The heme oxygenase 1 product biliverdin interferes with hepatitis C virus replication by increasing antiviral interferon response

“…Degradation of heme by heme oxygenases results in the production of carbon monoxide (CO), free iron, and biliverdin. HO‐1, in contrast to the isoforms HO‐2 and HO‐3, is inducible by various stimuli,12, 13 such as cobalt‐protoporphyrin‐IX (CoPP),14, 15 but also by hypoxia, which can be induced by, for example, high amounts of CO 16. Of the HO‐1 products, CO and biliverdin seem to be the major mediators of protective HO‐1 effects within the liver 17–19.…”