Interaction of methyl-xanthines with myeloperoxidase. An anti-inflammatory mechanism.
1. Inhibition of myeloperoxidase (MPO)-catalyzed reactions by methyl-substituted xanthines has been investigated. 2. Except for theobromine and caffeine, all xanthines tested were potent inhibitors of the MPO-H2O2-Cl- system. 3. In contrast to methyl substitution in the 1 or 8 position of xanthine, substitution in the 3 or 7 position had a marked effect on the inhibition of MPO catalysis. 4. Two different inhibitory mechanisms were induced; scavenging of hypochlorous acid (HOCl) generated by the MPO system and accumulation of Compound II (ferryl MPO) which is inactive as a catalyst of Cl- oxidation.
van Zyl
J M
JM
Department of Pharmacology, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
Kriegler
A
A
van der Walt
B J
BJ
D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D006801:Humans; D006997:Hypochlorous Acid / Q000378:metabolism; D009243:NAD / Q000378:metabolism; D010084:Oxidation-Reduction; D009195:Peroxidase / Q000037:antagonists & inhibitors*; D013057:Spectrum Analysis; D013329:Structure-Activity Relationship; D014970:Xanthines / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D014970:Xanthines; D009243:NAD; C008514:methylxanthine; D006997:Hypochlorous Acid; D009195:Peroxidase