Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Motterlini, Roberto; Haas, Benjamin; Foresti, Roberta

doi:10.1186/2045-9912-2-28

Medical Gas Research

Table 1 Effect of CO-RMs on in vitro and in vivo inflammatory disease models

From: Emerging concepts on the anti-inflammatory actions of carbon monoxide-releasing molecules (CO-RMs)

Type of CO-RM	Inflammatory disease models	Effect on inflammatory markers/	References
Type of CO-RM	*in vitroand in vivo*	Overall outcome	References
CORM-3	Vascular thrombosis in rats	↓ fibrinogen and fibrin	[18]
CORM-3	Vascular thrombosis in rats	↑ pro-thrombin	[18]
CORM-3	Hemorrhagic stroke induced by collagenase in rats	↓ TNF-α production	[19]
CORM-3	Hemorrhagic stroke induced by collagenase in rats	↓ brain injury	[19]
CORM-2	Polymicrobial sepsis induced by cecal ligation and perforation (CLP) in mice	↑ protein C system	[20]
		↓ plasma thrombomodulin
		↓ number of thrombi in liver, kidney and lung
CORM-3	Postmenopausal rheumatoid arthritis osteoporosis in mice	↓ cellular infiltration and cartilage degradation	[21]
		↓ TNF-α production
		↓ Serum levels of IL-6, alkaline phosphatase and
		MMP-3
CORM-2	Coagulation and fibrinolitic markers in human umbilical vein endothelial cells (HUVEC)	↓ tissue factor	[22]
CORM-2		↓ plasminogen activator inhibitor type 1 (PAI-1)	[22]
CORM-2	Neuropatic pain and microglia activation in mice induced by nerve injury	↓ mechanical allodynia	[23]
CORM-3		↓ thermal hyperalgesia
		↓ nNOS and iNOS expression
		↓ microglial marker (CD11b/c)
CORM-3	Vascular inflammation in human umbilical vein endothelial cells (HUVEC)	↓ VCAM-1 and ECAM expression	[24–26]
CORM-2		↓ NF-kβ and p38-MAPK expression
		↓ mitochondrial respiration
		↓ NF-kβ and iNOS expression
CORM-2	Ischemia-reperfusion injury after kidney transplantation in rats	↑ survival rate	[27]
CORM-3		↓ acute tubular necrosis and hemorrhage	[27]
CORM-2	Colitis induced by dextran sodium sulfate in mice	↓ disease activity index	[28]
		↓ myeloperoxidase (MPO) activity
		↓ TNF-α production
CORM-2	Endoplasmic reticulum (ER) stress induced by thapsigargin in human hepatocytes and mice	↓ C-reactive protein (CRP)	[29]
CORM-3		↓ serum amyloid P component (SAP)	[29]
CORM-2	Cutaneous wound healing in rats	↑ cell proliferation and wound contraction	[30]
		↑ collagen synthesis
		↓ TNF-α production and ICAM-1 expression
		↑ IL-10 production
CORM-2	Acute hepatic ischemia-reperfusion injury in rats	↑ anti-apoptotic protein Bcl2	[31]
		↓ markers of hepatic damage (AST/ALT)
		↓ serum levels of TNF-α and IL-6
		↓ caspase activity and NF-kβ expression
CORM-2	Acute pancreatitis in rats	↓ serum levels of TNF-α and IL-1β	[32]
		↓ NF-kβ expression and MPO activity
		↑ IL-10 production
CORM-3	Rheumatoid arthritis induced by KBxN serum transfer in mice	↑ serum osteocalcin and HO-1 expression	[33]
		↓ MMP-9, MMP-13 and IL-1β expression
		↓ high mobility group box 1 (HMGB1)
		↓ Receptor activator of nuclear factor κB ligand (RANKL)
CORM-2	Ischemia-reperfusion induced inflammation of small intestine in mice	↓ TNF-α and ICAM expression	[34]
		↓ leukocytes rolling and adhesion
		↓ NF-kβ expression and MPO activity
CORM-2	Inflammatory response induced by lipopolysaccharide in RAW 264.7 macrophages and BV-2 microglia	↓ iNOS mRNA and protein expression	[35]
		↑ COX-2 expression and NF-kβ expression
		↑ PGE2 levels
		↑ phosphorylation of Akt and MAPKs
CORM-2	Sepsis induced by cecal ligation and puncture (CLP) in mice	↓ neutrophil infiltration in broncoalveolar lavage and liver	[36–39]
		↓ MPO activity in lung and NF-kβ in liver
		↓ serum TNF-α and high mobility group box 1 (HMGB1)
		↓ nitrite/nitrate plasma levels
		↑ cardiac PGC-1α and mitochondrial biogenesis
CORM-A1	Inflammatory response induced by TNF- α in brain vascular endothelial cells	↓ NADPH oxidase activity	[40]
CORM-A1		↓ apoptosis	[40]
CORM-3	Post-operative ileus in mice	↑ intestinal contractility and transit	[41]
CORM-A1		↑ intestinal contractility and transit
		↑ IL-10 and HMOX1 expression
		↓ IL-6 and iNOS expression
		↓ leukocyte infiltration
CORM-2	Inflammatory response in liver and small intestine of thermally injured mice	↓ TNF-α, IL-1β and iNOS expression	[42, 43]
		↓ leukocyte infiltration
		↓ NF-kβ and ICAM-1 expression
CORM-3	Bacterial activity in vitro and bacterial infection in vivo	↓ E. Coli and P. Aeuruginosa growth in vitro	[17, 44–48]
CORM-2		↑ bacteriostatic and bactericidal effects in vivo
CORM-A1		↑ increased phagocytosis in vivo
CORM-371		↑ increased phagocytosis in vivo
CORM-371		↓ respiration in bacteria
ALF-021		↑ survival after bacterial infection in vivo
ALF-062		↓ high mobility group box 1 (HMGB1)
CORM-3	Collagen-induced arthritis in mice	↓ prostaglandin E2 (PGE2)	[49]
		↓ pro-inflammatory interleukins (IL-1β, IL-2, IL-6)
		↑ anti-inflammatory interleukins (IL-10)
		↓ expression of cyclooxygenase-2 (COX-2)
CORM-3	Vascular inflammation in human neutrophils and rat primary endothelial (EC) and mast (MC) cells	↓ oxidative burst in human PMNs	[50]
		↓ expression of CD54 in rat ECs
		↓ histamine in MCs
CORM-2	Inflammatory response induced by pro-inflammatory cytokines in Caco-2 cells and human chondrocytes	↓ prostaglandin E2 (PGE2) and nitrite	[51–53]
		↓ ROS production
		↓ COX-2 and iNOS protein expression
		↓ NF-kβ expression
		↓ metalloproteinase-7 (MMP-7)
CORM-3	Leukocyte-endothelial interaction in vitro and in a models of acute pancreatitis and paw edema in mice	↓ PMNs leukocytes in peritoneal cavity	[54]
CORM-A1		↓ PMNs leukocytes in peritoneal cavity
		↓ PMNs rolling on endothelial cells
		↓ paw edema and swelling
CORM-3	Inflammatory response induced by LPS/INFγ and hypoxia in BV2 microglia cells	↓ nitrite and TNF-α production	[55, 56]
CORM-3		↓ hypoxia-reoxygenation damage	[55, 56]
CORM-2	Inflammatory response induced by lipopolysaccharide in RAW 264.7 macrophages	↓ nitrite and TNF-α production	[57]
CORM-3		↓ nitrite and TNF-α production	[57]

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ISSN: 2045-9912

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