Document Detail

Inactivation of creatine kinase during the interaction of mefenamic acid with horseradish peroxidase and hydrogen peroxide: participation by the mefenamic acid radical.
MedLine Citation:
PMID:  12597989     Owner:  NLM     Status:  MEDLINE    
Creatine kinase (CK) was used as a marker molecule to examine the side effects of damage to tissues by mefenamic acid, an effective drug to treat rheumatic and arthritic diseases, with horseradish peroxidase and hydrogen peroxide (HRP-H(2)O(2)). Mefenamic acid inactivated CK during its interaction with HRP-H(2)O(2). Also, diphenylamine and flufenamic acid caused a loss of CK activity, indicating the imino group, not substituent groups, in the phenyl rings have a crucial role in CK inactivation. Rapid change in mefenamic acid spectra was detected, suggesting that mefenamic acid is efficiently oxidized by HRP-H(2)O(2). Peroxidases oxidize xenobiotics to free radicals by a one-electron transfer. However, direct detection of mefenamic acid radicals by electron spin resonance (ESR) was unsuccessful. Reduced glutathione and 5,5-dimethyl-1-pyrroline-1-oxide (DMPO) in the reaction mixture containing mefenamic acid with HRP-H(2)O(2) produced ESR signals consistent with a DMPO-glutathionyl radical adduct. These results suggest that inactivation of CK is probably caused through formation of mefenamic acid radicals. Sulfhydryl groups and tryptophan residues of CK were diminished by mefenamic acid with HRP-H(2)O(2). Other SH enzymes, including alcohol dehydrogenase and glyceraldehyde-3-phosphate dehydrogenase, were very sensitive to mefenamic acid with HRP-H(2)O(2). Inactivation of SH enzymes may explain some deleterious actions of mefenamic acid.
Sanae Muraoka; Toshiaki Miura
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Life sciences     Volume:  72     ISSN:  0024-3205     ISO Abbreviation:  Life Sci.     Publication Date:  2003 Mar 
Date Detail:
Created Date:  2003-02-24     Completed Date:  2003-03-17     Revised Date:  2003-11-14    
Medline Journal Info:
Nlm Unique ID:  0375521     Medline TA:  Life Sci     Country:  England    
Other Details:
Languages:  eng     Pagination:  1897-907     Citation Subset:  IM    
Hokkaido College of Pharmacy, Katsuraoka-cho 7-1, Otaru 047-0264, Japan.
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MeSH Terms
Amino Acid Substitution
Anti-Inflammatory Agents, Non-Steroidal / chemistry,  pharmacology*
Creatine Kinase / antagonists & inhibitors*
Electron Spin Resonance Spectroscopy
Enzyme Inhibitors / chemistry,  pharmacology*
Free Radicals
Horseradish Peroxidase / pharmacology*
Hydrogen Peroxide / pharmacology*
Mefenamic Acid / chemistry,  pharmacology*
Muscle, Skeletal / drug effects,  enzymology
Oxidants / pharmacology*
Reg. No./Substance:
0/Anti-Inflammatory Agents, Non-Steroidal; 0/Enzyme Inhibitors; 0/Free Radicals; 0/Oxidants; 61-68-7/Mefenamic Acid; 7722-84-1/Hydrogen Peroxide; EC 1.11.1.-/Horseradish Peroxidase; EC Kinase

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