Anti-oxidant actions of oxymethazoline and xylomethazoline

Westerveld, Gerrit-Jan; Scheeren, R. A.; Dekker, Ingrid; Griffioen, D. H.; Voss, Hans–Peter; Bast, Aalt

doi:10.1016/0922-4106(95)90185-x

Cited by 18 publications

(18 citation statements)

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“…Furthermore, Westerveld et al (2000) referred that 0.3 mM oxymetazoline inhibited inducible nitric oxide synthase in a cellular system with rat alveolar macrophage cell line NR 8383, whereas the constitutive nitric oxide synthase was not affected. Oxymetazoline was also a potent inhibitor of lipid peroxidation and excellent hydroxyl radical scavenger (Westerveld et al, 1995). In a cell-free model of microsomal lipid peroxidation, consisting of Fe 2ϩ /ascorbic acid and liver microsomes, oxymetazoline inhibited lipid peroxidation completely at concentrations between 0.015 and 0.02 mM (Westerveld et al, 1995).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, Westerveld et al (2000) showed that oxymetazoline strongly inhibits the expression of the inducible form of nitric oxide synthase and speculated that nasal decongestants might offer a new tool to reduce inflammatory mechanisms. Westerveld et al (1995) also referred to antioxidant actions of oxymetazoline by showing that this compound is a potent inhibitor of microsomal lipid peroxidation and an excellent hydroxyl radical scavenger.…”

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confidence: 99%

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

Beck‐Speier¹,

Dayal²,

Karg³

et al. 2005

J Pharmacol Exp Ther

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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.

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

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

Beck‐Speier¹,

Dayal²,

Karg³

et al. 2005

J Pharmacol Exp Ther

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“…Recently the distinct antioxidant properties of oxymetazoline and xylometazoline i.e. hydroxyl radical scavenging and lipid peroxidation inhibition have been reported [19].…”

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confidence: 99%

Inhibition of nitric oxide synthase by nasal decongestants

Westerveld¹,

Voss²,

Hee³

et al. 2000

Eur Respir J

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The nasal decongestants oxymetazoline and xylometazoline are frequently used in the topical treatment of rhinitis and sinusitis. As nitric oxide (NO) is thought to play a role in inflammation of the upper respiratory tract, the aim of this study was to examine the in vitro effects of these compounds on the activity and the expression of NO producing enzymes, including the inducible form of NO synthase (iNOS) and the constitutive isoform of NO synthase (cNOS).Experiments concerning the effects of both compounds on enzymatic activity and enzyme induction of iNOS were performed in a lipopolysaccharide (LPS) induced rat alveolar macrophage cell line (NR8383) using the Griess assay and the 3 H-citrulline assay respectively. The effects on cNOS were examined in fresh rat synaptosomes using the 3 H-citrulline assay. The direct scavenging properties of both compounds were investigated using a amperometric NO sensor.Oxymetazoline and xylometazoline were shown to have a dose dependent inhibitory effect on total iNOS activity indicated by nitrite/nitrate formation in the Griess assay. This effect was found to be due to an inhibition of induction of the enzyme rather than inhibition of the enzyme activity, as was investigated in two separate experiments using the 3 H-citrulline assay. Inhibition of cNOS was moderate and in the same order of magnitude as the inhibition of enzymatic iNOS activity. Direct scavenging of NO could not be detected.As constitutive nitric oxide synthase activity is thought to serve beneficial physiological functions, and exaggerated inducible nitric oxide synthase activity may cause exacerbation of the inflammatory process, pharmacological treatment influencing the nitric oxide generating system should focus on inhibition of inducible nitric oxide synthase alone. The specific characteristics of these decongestants in vitro suggests suitability for this application and may indicate an additional beneficial effect in the treatment of upper respiratory tract inflammation. Eur Respir J 2000; 16: 437±444.

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“…In the same time, other authors demonstrated the benefit of oxymetazoline above all, and xylometazoline somewhat less, in the topical treatment of nasal inflammation of rhinitis, due to its antioxidant properties (Westerveld et al, 1995).…”

Section: Vasoconstrictors (α-Adrenergics)mentioning

confidence: 87%