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Inactivation of α 1 ‐Antiproteinase Induced by Phenylbutazone: Participation of Peroxyl Radicals and Hydroperoxide
Author(s) -
Muraoka Sanae,
Miura Toshiaki
Publication year - 2006
Publication title -
basic and clinical pharmacology and toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.805
H-Index - 90
eISSN - 1742-7843
pISSN - 1742-7835
DOI - 10.1111/j.1742-7843.2006.pto_473.x
Subject(s) - phenylbutazone , chemistry , horseradish peroxidase , catalase , radical , peroxidase , biochemistry , enzyme , pharmacology , biology
To clarify the action of a side‐effect of phenylbutazone, we investigated the inactivation of α 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 α 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 α 1 ‐antiproteinase inactivation induced by phenylbutazone. Oxidation of phenylbutazone was stopped by catalase, but the inactivation reaction of α 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 α 1 ‐antiproteinase. Other anti‐inflammatory drugs did not inactivate α 1 ‐antiproteinase during interaction with HRP‐H 2 O 2 . Inactivation of α 1 ‐antiproteinase may contribute to serious side effects of phenylbutazone.