title: Carbon monoxide-releasing molecules: a pharmacological expedient to counteract inflammation.
abstract: 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.
authors.affiliation: Department of Pharmacology, University of Valencia, Av. Vicent Andres Estelles s/n, 46100 Burjassot, Valencia, Spain. maria.j.alcaraz@uv.es
authors.forename: María José
authors.initials: MJ
authors.lastname: Alcaraz
authors.forename: María Isabel
authors.initials: MI
authors.lastname: Guillen
authors.forename: María Luisa
authors.initials: ML
authors.lastname: Ferrandiz
authors.forename: Javier
authors.initials: J
authors.lastname: Megías
authors.forename: Roberto
authors.initials: R
authors.lastname: Motterlini
mesh_terms: 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
chemical_list: 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