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CELLULAR AND MOLECULAR

Oxymetazoline Inhibits Proinflammatory Reactions: Effect on Arachidonic Acid-Derived Metabolites

GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, Neuherberg/Munich, Germany (I.B.-S., N.D., E.K., K.L.M., G.S., M.S.); and Merck Selbstmedikation GmbH, Darmstadt, Germany (S.M.K.)

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 A₂ (PLA₂) activity, respiratory burst and synthesis of prostaglandin E₂ (PGE₂), 15(S)-hydroxy-eicosatetraenoic acid (15-HETE), leukotriene B₄ (LTB₄), 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 PLA₂ activity and 15-HETE at 1 mM, enhanced PGE₂ at 0.1 mM, strongly inhibited LTB₄ 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 PLA₂ activity and PGE₂ and 15-HETE formation in AMs but inhibited UCP-induced LTB₄ 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 LTB₄ formation and respiratory burst at 0.1 mM (p < 0.05). In conclusion, in canine AMs, oxymetazoline suppressed proinflammatory reactions including 5-LO activity, LTB₄ formation, and respiratory burst and prevented particle-induced oxidative stress, whereas PLA₂ activity and synthesis of immune-modulating PGE₂ and 15-HETE were not affected.

Address correspondence to: Dr. Ingrid Beck-Speier, GSF-National Research Center for Environment and Health, Institute for Inhalation Biology, Ingolstädter Landstrasse 1, D-85764 Neuherberg/Munich, Germany. E-mail: beck-speier{at}gsf.de

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				S. D. Shanler and A. L. Ondo Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective {alpha}1-Adrenergic Receptor Agonist, Oxymetazoline Arch Dermatol, November 1, 2007; 143(11): 1369 - 1371. [Full Text] [PDF]