Abstract:
: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.
journal_name
Basic Clin Pharmacol Toxicoljournal_title
Basic & clinical pharmacology & toxicologyauthors
Muraoka S,Miura Tdoi
10.1111/j.1742-7843.2006.pto_473.xsubject
Has Abstractpub_date
2006-09-01 00:00:00pages
261-6issue
3eissn
1742-7835issn
1742-7843pii
PTOpto_473journal_volume
99pub_type
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