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 Ͻ 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 Ͻ 0.05). In opsonized zymosanstimulated AMs, oxymetazoline inhibited LTB 4 formation and respiratory burst at 0.1 mM (p Ͻ 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.

Oxymetazoline adds to the effectiveness of fluticasone furoate in the treatment of perennial allergic rhinitis

“…In addition to being an a-agonist, oxymetazoline has been shown to have various antioxidative and anti-inflammatory properties. [8][9][10][11][12] Whether any of these effects contributed to our results is unknown. The oxymetazoline was dosed once daily at night.…”

Successful Treatment of the Erythema and Flushing of Rosacea Using a Topically Applied Selective α1-Adrenergic Receptor Agonist, Oxymetazoline

“…In upper respiratory tract infections, oxymetazoline and xylometazoline have been shown to inhibit neutrophilic phagocytosis and oxidative burst, resulting in a decrease in microbial killing, decreased generation of proinflammatory cytokines, and decreased inflammation. 16,17 Oxymetazoline has also recently been shown to have significant effects on the arachidonic acid cascade, strongly inhibiting 5-lipoxygenase activity and thus decreasing the synthesis of the highly proinflammatory leukotriene B 4 . 17 A potential clinical role for oxymetazoline, or other agents of this class, as inhibitors of inflammation and oxidative-stress dependent reactions in inflammatory and/or infectious skin conditions is intriguing but has yet to be investigated.…”

Combination of mometasone furoate and oxymetazoline for the treatment of adenoid hypertrophy concomitant with allergic rhinitis: A randomized controlled trial

“…OXY has been demonstrated to have various antioxidant and anti-inflammatory properties in addition to its potent decongestive effect2425. Previous studies have demonstrated that the concomitant administration of MF and OXY may provide better improvements in AR patients, especially those with nasal congestion symptom262728293031.…”