Carbon monoxide-releasing molecules: a pharmacological expedient to counteract inflammation.
Carbon monoxide (CO) mediates many of the biological effects that are attributed to heme oxygenase (HO), the enzyme responsible for CO production in mammals. Antioxidant and anti-inflammatory activities of HO-1, the inducible isoform of heme oxygenase, have been demonstrated in a variety of disease models and a therapeutic exploitation of this pathway is currently under scrutiny. In this context, the liberation of CO from CO-releasing molecules (CO-RMs) is extremely attractive as these compounds may form the basis of a new class of pharmaceuticals. Recent investigations indicate that HO-1 and CO modulate important processes in chronic inflammation; these include the control of immune responses, the production of inflammatory mediators and the mitigation of cartilage or bone destruction. As HO-1 is highly expressed in the joint tissues of patients affected by arthritic diseases, it is plausible to suggest that this pathway may play a protective role against joint degenerative diseases. Studies aimed at identifying the signaling pathways responsive to endogenous CO and CO-RMs in rheumatoid arthritis and other inflammatory states are currently in progress. This research will help to elucidate the molecular mechanisms underlying the pharmacological effects of CO-RMs and may lead to the development of novel therapeutic strategies for the treatment of acute and chronic inflammatory conditions.
Alcaraz
María José
MJ
Department of Pharmacology, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain. maria.j.alcaraz@uv.es
Guillen
María Isabel
MI
Ferrandiz
María Luisa
ML
Megías
Javier
J
Motterlini
Roberto
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000188:drug therapy; D002248:Carbon Monoxide / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000378:metabolism; D045726:Metalloproteases / Q000378:metabolism; D009942:Organometallic Compounds / Q000494:pharmacology / Q000627:therapeutic use; D010003:Osteoarthritis / Q000188:drug therapy; D018384:Oxidative Stress; D012428:Ruthenium; D015398:Signal Transduction
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D009942:Organometallic Compounds; C476530:tricarbonylchloro(glycinato)ruthenium(II); C447082:tricarbonyldichlororuthenium (II) dimer; D002248:Carbon Monoxide; D012428:Ruthenium; D051547:Heme Oxygenase-1; D045726:Metalloproteases