Inactivation of alpha1-antiproteinase induced by phenylbutazone: participation of peroxyl radicals and hydroperoxide.
To clarify the action of a side-effect of phenylbutazone, we investigated the inactivation of alpha(1)-antiproteinase induced by phenylbutazone in the presence of horseradish peroxidase (HRP) and H(2)O(2) (HRP-H(2)O(2)). The activity of alpha(1)-antiproteinase was rapidly lost during the interaction of phenylbutazone with HRP-H(2)O(2) under aerobic conditions. Phenylbutazone showed a marked spectral change under aerobic conditions but not under anaerobic conditions. Spin trap agents were very effective in inhibiting alpha(1)-antiproteinase inactivation induced by phenylbutazone. Oxidation of phenylbutazone was stopped by catalase, but the inactivation reaction of alpha(1)-antiproteinase proceeded even after removal of H(2)O(2) in the reaction mixture. Formation of the peroxidative product from phenylbutazone was detected by iodometric assay. These results indicate that both peroxyl radicals and the peroxidative product of phenylbutazone participated in the inactivation of alpha(1)-antiproteinase. Other anti-inflammatory drugs did not inactivate alpha(1)-antiproteinase during interaction with HRP-H(2)O(2). Inactivation of alpha(1)-antiproteinase may contribute to serious side effects of phenylbutazone.
Muraoka
Sanae
S
Hokkaido Pharmaceutical University, Otaru 047-0264, Japan.
Miura
Toshiaki
T
D000596:Amino Acids / Q000378:metabolism; D016166:Free Radical Scavengers; D005609:Free Radicals / Q000378:metabolism*; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism*; D015394:Molecular Structure; D010653:Phenylbutazone / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D013997:Time Factors; D000515:alpha 1-Antitrypsin / Q000378:metabolism*
D000596:Amino Acids; D016166:Free Radical Scavengers; D005609:Free Radicals; D015842:Serine Proteinase Inhibitors; D000515:alpha 1-Antitrypsin; D006861:Hydrogen Peroxide; D010653:Phenylbutazone