Inactivation of α1-Antiproteinase Induced by Phenylbutazone: Participation of Peroxyl Radicals and Hydroperoxide

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Abstract:

Abstract:

To clarify the action of a side-effect of phenylbutazone, we investigated the inactivation of α1-antiproteinase induced by phenylbutazone in the presence of horseradish peroxidase (HRP) and H2O2 (HRP-H2O2). The activity of α1-antiproteinase was rapidly lost during the interaction of phenylbutazone with HRP-H2O2 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 α1-antiproteinase inactivation induced by phenylbutazone. Oxidation of phenylbutazone was stopped by catalase, but the inactivation reaction of α1-antiproteinase proceeded even after removal of H2O2 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 α1-antiproteinase. Other anti-inflammatory drugs did not inactivate α1-antiproteinase during interaction with HRP-H2O2. Inactivation of α1-antiproteinase may contribute to serious side effects of phenylbutazone.

Document Type: Research Article

DOI: http://dx.doi.org/10.1111/j.1742-7843.2006.pto_473.x

Affiliations: Hokkaido Pharmaceutical University, Katsuraoka-cho 7-1, Otaru 047-0264, Japan

Publication date: September 1, 2006

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  • Formerly Pharmacology & Toxicology
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