Anti-oxidant actions of oxymethazoline and xylomethazoline.
Anti-oxidant actions of oxymethazoline and xylomethazoline were investigated by measuring inhibition of microsomal lipid peroxidation and hydroxyl radical scavenging activity. Oxymethazoline was shown to be a potent inhibitor of lipid peroxidation (IC50 = 4.9 microM at t = 15 min, IC50 = 8.1 microM at t = 30 min), in contrast to xylomethazoline. Both compounds were excellent hydroxyl radical scavengers. Their rate constants (ks = 1.1 x 10(12) M-1 s-1 for oxymethazoline and ks = 4.7 x 10(10) M-1 s-1 for xylomethazoline) exceeded the rate constant of a known powerful scavenger cimetidine (ks = 1.8 x 10(10) M-1 s-1). The difference in inhibiting lipid peroxidation might be explained by the fact that only oxymethazoline has a hydroxy group which can donate a hydrogen atom and terminate the chain reaction of lipid peroxidation. The mechanism of hydroxyl radical scavenging activity is still unclear. Moreover oxymethazoline seems to have a different mode of action in scavenging hydroxyl radicals than xylomethazoline and cimetidine which results in an extremely high rate constant. Because oxidants play a role in tissue damage in inflammation, it was hypothesized that especially oxymethazoline and to a lesser extent xylomethazoline may have an additional beneficial effect, due to their anti-oxidant properties, in the topical treatment of nasal inflammation.
Leiden/Amsterdam Center for Drug Research, Department of Pharmacochemistry, Vrije Universiteit, Netherlands.
G J
GJ
Westerveld
R A
RA
Scheeren
I
I
Dekker
D H
DH
Griffioen
H P
HP
Voss
A
A
Bast
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D002927:Cimetidine / Q000494:pharmacology; D016166:Free Radical Scavengers / Q000494:pharmacology; D006635:Histamine H2 Antagonists / Q000494:pharmacology; D017665:Hydroxyl Radical / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D066298:In Vitro Techniques; D007700:Kinetics; D015227:Lipid Peroxidation / Q000187:drug effects; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism; D010109:Oxymetazoline / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism
D000975:Antioxidants; D016166:Free Radical Scavengers; D006635:Histamine H2 Antagonists; D007093:Imidazoles; D017382:Reactive Oxygen Species; D017665:Hydroxyl Radical; D002927:Cimetidine; D010109:Oxymetazoline; C009695:xylometazoline