title: Oxymetazoline inhibits proinflammatory reactions: effect on arachidonic acid-derived metabolites.
abstract: The nasal decongestant oxymetazoline effectively reduces rhinitis symptoms. We hypothesized that oxymetazoline affects arachidonic acid-derived metabolites concerning inflammatory and oxidative stress-dependent reactions. The ability of oxymetazoline to model pro- and anti-inflammatory and oxidative stress responses was evaluated in cell-free systems, including 5-lipoxygenase (5-LO) as proinflammatory, 15-lipoxygenase (15-LO) as anti-inflammatory enzymes, and oxidation of methionine by agglomerates of ultrafine carbon particles (UCPs), indicating oxidative stress. In a cellular approach using canine alveolar macrophages (AMs), the impact of oxymetazoline on phospholipase A(2) (PLA(2)) activity, respiratory burst and synthesis of prostaglandin E(2) (PGE(2)), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B(4) (LTB(4)), and 8-isoprostane was measured in the absence and presence of UCP or opsonized zymosan as particulate stimulants. In cell-free systems, oxymetazoline (0.4-1 mM) inhibited 5-LO but not 15-LO activity and did not alter UCP-induced oxidation of methionine. In AMs, oxymetazoline induced PLA(2) activity and 15-HETE at 1 mM, enhanced PGE(2) at 0.1 mM, strongly inhibited LTB(4) and respiratory burst at 0.4/0.1 mM (p < 0.05), but did not affect 8-isoprostane formation. In contrast, oxymetazoline did not alter UCP-induced PLA(2) activity and PGE(2) and 15-HETE formation in AMs but inhibited UCP-induced LTB(4) formation and respiratory burst at 0.1 mM and 8-isoprostane formation at 0.001 mM (p < 0.05). In opsonized zymosan-stimulated AMs, oxymetazoline inhibited LTB(4) formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB(4) formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA(2) activity and synthesis of immune-modulating PGE(2) and 15-HETE were not affected.
authors.affiliation: GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg/Munich, Germany. beck-speier@gsf.de
authors.forename: Ingrid
authors.initials: I
authors.lastname: Beck-Speier
authors.forename: Niru
authors.initials: N
authors.lastname: Dayal
authors.forename: Erwin
authors.initials: E
authors.lastname: Karg
authors.forename: Konrad L
authors.initials: KL
authors.lastname: Maier
authors.forename: Gabriele
authors.initials: G
authors.lastname: Schumann
authors.forename: Manuela
authors.initials: M
authors.lastname: Semmler
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Koelsch
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism*; D002244:Carbon; D002478:Cells, Cultured; D004285:Dogs; D016859:Lipoxygenase Inhibitors; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D014663:Nasal Decongestants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D010109:Oxymetazoline / Q000494:pharmacology*; D010316:Particle Size; D010587:Phagocytosis; D016897:Respiratory Burst / Q000187:drug effects*; D015054:Zymosan
chemical_list: D016859:Lipoxygenase Inhibitors; D014663:Nasal Decongestants; D016718:Arachidonic Acid; D002244:Carbon; D010109:Oxymetazoline; D015054:Zymosan