2006 Fiscal Year Final Research Report Summary
Studies on non-steroidal anti-inflammatory drugs-induced gastrointestinal damage: Participation in free radicals.
| Project/Area Number |
15590065
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Biological pharmacy
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| Research Institution | Hokkaido Pharmaceutical University School of Pharmacy |
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Principal Investigator |
MIURA Toshiaki Pharmaceutical Faculty, Biology, Professor, 薬学部, 教授 (00094855)
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| Co-Investigator(Kenkyū-buntansha) |
MURAOKA Sanae Pharmaceutical Faculty, Biology, lecturer, 薬学部, 講師 (20347793)
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| Project Period (FY) |
2003 – 2006
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| Keywords | Non-steroidal anti-inflammatory drugs / gastrointestinal lesion / peroxidase / free radical / sulfhydryl group / lipid peroxidation / prostaglandin H synthase / cyclooxygenase |
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| Research Abstract |
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used to treat inflammatory diseases, including rheumatoid arthritis and gout. The anti-inflammatory action of NSAIDs is due to the inhibition of prostaglandin synthesis by preventing cyclooxygenase (COX) activity of prostaglandin H synthase (PGS). However, administration of NSAIDs causes gastrointestinal mucosal lesions and a decrease in granulocytes as side effects. PGS catalyzes two distinct enzyme reactions: (1) bis-dioxygenation of arachidonic acid catalyzed by COX activity of PGS to form PGG_2; (2) reduction of the hydroperoxide group in PGG_2 by PGS hydroperoxidase. Most NSAID are oxidized by peroxidases to produce NSAID radicals that damage biological components, such as lipids and enzymes. Indomethacin, phenylbutazone and piroxicam are more toxic under aerobic conditions than anaerobic conditions during the interaction with peroxidase. We indicate the contribution of peroxidases in the formation of gastrointestinal mucosal lesions induced by NSAIDs.
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Research Products
(4 results)
