title: Effect of anti-inflammatory drugs on myeloperoxidase-dependent hydroxyl radical generation by human neutrophils.
abstract: Neutrophils comprise a group of leukocytes that play a pivotal role in inflammation and vascular diseases like ischemia/reperfusion. These activated phagocytic cells are drawn to the site of injury, secreting superoxide and other oxidants derived from the formation of this free radical. This series of events frequently results in localized tissue damage. Surprisingly, free radical scavengers frequently offer only minimal relief. Why this is so may be due, in part, to our limited understanding of mechanisms that govern generation of free radicals in these settings. Although the metal ion-catalyzed Haber-Weiss reaction is considered the classical pathway for neutrophil-derived hydroxyl radical, an alternative mechanism, such as the myeloperoxidase-dependent pathway, may undoubtedly contribute to the formation of this free radical by stimulated neutrophils. In this study, we explored this possibility by investigating the role of different classes of anti-inflammatory drugs to ameliorate hydroxyl radical generation via the myeloperoxidase-dependent pathway. In this paper, we report that meclofenamic acid inhibited myeloperoxidase-dependent hydroxyl radical generation through scavenging of hypochlorous acid and not by direct inhibition of myeloperoxidase. The importance of these results with regard to the clinical efficacy of this anti-inflammatory compound remains to be determined as studies into the significance of myeloperoxidase-dependent hydroxyl radical formation in inflammatory tissue injury continue.
authors.affiliation: Department of Pharmaceutical Sciences, University of Maryland School of Pharmacy, Baltimore 21201, USA.
authors.forename: C L
authors.initials: CL
authors.lastname: Ramos
authors.forename: S
authors.initials: S
authors.lastname: Pou
authors.forename: G M
authors.initials: GM
authors.lastname: Rosen
mesh_terms: D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D017665:Hydroxyl Radical / Q000378:metabolism*; D006997:Hypochlorous Acid / Q000737:chemistry; D008469:Meclofenamic Acid / Q000737:chemistry / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009195:Peroxidase / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; D017665:Hydroxyl Radical; D008469:Meclofenamic Acid; D006997:Hypochlorous Acid; D009195:Peroxidase