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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
in vitroand in vivo Overall outcome
CORM-3 Vascular thrombosis in rats ↓ fibrinogen and fibrin [18]
↑ pro-thrombin
CORM-3 Hemorrhagic stroke induced by collagenase in rats ↓ TNF-α production [19]
↓ brain injury
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
CORM-2 Coagulation and fibrinolitic markers in human umbilical vein endothelial cells (HUVEC) ↓ tissue factor [22]
↓ plasminogen activator inhibitor type 1 (PAI-1)
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 [2426]
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
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)
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 [3639]
↓ 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]
↓ apoptosis
CORM-3 Post-operative ileus in mice ↑ intestinal contractility and transit [41]
↑ 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, 4448]
CORM-2 ↑ bacteriostatic and bactericidal effects in vivo
CORM-A1 ↑ increased phagocytosis in vivo
↓ 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 [5153]
↓ 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]
↓ 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]
↓ hypoxia-reoxygenation damage
CORM-2 Inflammatory response induced by lipopolysaccharide in RAW 264.7 macrophages ↓ nitrite and TNF-α production [57]