title: Interaction of methyl-xanthines with myeloperoxidase. An anti-inflammatory mechanism.
abstract: 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.
authors.affiliation: Department of Pharmacology, Faculty of Medicine, University of Stellenbosch, Tygerberg, South Africa.
authors.forename: J M
authors.initials: JM
authors.lastname: van Zyl
authors.forename: A
authors.initials: A
authors.lastname: Kriegler
authors.forename: B J
authors.initials: BJ
authors.lastname: van der Walt
mesh_terms: 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*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014970:Xanthines; D009243:NAD; C008514:methylxanthine; D006997:Hypochlorous Acid; D009195:Peroxidase