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Phenylbutazone radicals inactivate creatine kinase.
- Source :
-
Free radical research [Free Radic Res] 2001 Feb; Vol. 34 (2), pp. 167-75. - Publication Year :
- 2001
-
Abstract
- Creatine kinase (CK) was used as a marker molecule to examine the side effect of damage to tissues by phenylbutazone (PB), an effective drug to treat rheumatic and arthritic diseases, with horseradish peroxidase and hydrogen peroxide (HRP-H(2)O2). PB inactivated CK during its interaction with HRP-H(2) O(2), and inactivated CK in rat heart homogenate. PB carbon-centered radicals were formed during the interaction of PB with HRP-H(2)O2. The CK efficiently reduced electron spin resonance signals of the PB carbon-centered radicals. The spin trap agent 2-methyl-2-nitrosopropane strongly prevented CK inactivation. These results show that CK was inactivated through interaction with PB carbon-centered radicals. Sulfhydryl groups and tryptophan residues in CK were lost during the interaction of PB with HRP-H(2)O2, suggesting that cysteine and tryptophan residues are oxidized by PB carbon-centered radicals. Other enzymes, including alcohol dehydrogenase, glyceraldehyde-3-phosphate dehydrogenase, but not lactate dehydrogenase, were also inactivated. Sulfhydryl enzymes seem to be sensitive to attack by PB carbon-centered radicals. Inhibition of SH enzymes may explain some of the deleterious effects induced by PB.
- Subjects :
- Alcohol Dehydrogenase antagonists & inhibitors
Animals
Anti-Inflammatory Agents, Non-Steroidal adverse effects
Biomarkers
Cysteine metabolism
Free Radicals
Glyceraldehyde-3-Phosphate Dehydrogenases antagonists & inhibitors
Horseradish Peroxidase metabolism
Hydrogen Peroxide metabolism
L-Lactate Dehydrogenase antagonists & inhibitors
Male
Myocardium enzymology
Nitroso Compounds pharmacology
Oxidants pharmacology
Oxidation-Reduction
Oxidative Stress
Peroxidases metabolism
Phenylbutazone adverse effects
Prostaglandin-Endoperoxide Synthases metabolism
Rabbits
Rats
Rats, Wistar
Spin Labels
Swine
Tryptophan metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Creatine Kinase antagonists & inhibitors
Phenylbutazone pharmacology
Sulfhydryl Compounds metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1071-5762
- Volume :
- 34
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Free radical research
- Publication Type :
- Academic Journal
- Accession number :
- 11264893
- Full Text :
- https://doi.org/10.1080/10715760100300151