炎症
Online ISSN : 1884-4006
Print ISSN : 0389-4290
ISSN-L : 0389-4290
インドメタシンプロドラッグの好中球スーパーオキシド産生に及ぼす影響―アセメタシン, インドメタシンファルネシル, プログルメタシン, CP-331―
丹羽 雅之河野 健一小林 雅司野崎 正勝鶴見 介登
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1993 年 13 巻 5 号 p. 477-482

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As it has been known that non-steroidal anti-inflammatory drugs have damaging effect on gastric mucosa which may be related to superoxide production by neutrophils as indicated in recent reports, we evaluated the effect of indomethacin prodrugs (acemetacin, indomethacin-farnesil, prog-lumetacin and CP-331) on the superoxide production in rabbit neutrophils. Superoxide production was measured by chemiluminescence technique using a luciferine analogue (FCLA) . Proglunetacin inhibited PMA-induced, but not f-MLP-induced, superoxide production in a dose dependent manner. CP-331 depressed both f-MLP- and PMA-induced superoxide production. However, acemetacin and indomethacin-farnesil, and also their metabolite, indomethacin, did not inhibit these superoxide productions. All these compounds did not show any inhibitory effect on superoxide production derived from the hypoxanthine-xanthine oxidase system.
The results indicated that proglumetacin and CP-331 did not act as superoxide radical scavenger. CP - 331, but not other compounds, inhibited NADPH oxidase activity in rabbit neutrophils. CP-331 and proglumetacin showed only weak inhibition on the protein kinase C activity. From these results, proglumetacin and CP-331, but not acemetacin and indomethacin-farnesil, expressed inhibitory properties for superoxide production in neutrophils, although we could not decide their target sites.
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© 日本炎症・再生医学会
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