Effects of TZI-41127, inhibitor of 5-1ipoxygenase, and TZI-41078,dual inhibitor of 5-1ipoxygenase and cyclooxygenase, on active oxygen production

• Published in: Japanese Journal of Pharmacology 1988, Vol.46 (suppl), p.296-296
• Main Authors: Kobayashi, Motohiro, Nozaki, Masakatsu, Tsurumi, Kaito, Mikami, Takashi, Miyasaka, Katsuhiko
• Format: Article
• Language: English
• ISSN: 0021-5198; 1347-3506
• DOI: 10.1016/S0021-5198(19)57729-0

Effects of TZI-41127 and TZI-41078 on active oxygen production were compared with those of BW755C. (1)Active oxygen production of peripheral blood polymorphonuclear lenkocytes and peritoneal exudate cells stimulated by zymosan were evaluated using luminol-dependent chemiluminescence(LDCL) . TZI-41127, TZI-41078 and BW755C suppressed the LDCL from both inflammatory cells(50μM ; 95%, 100%, 88%, respectively) . But, nonsteroidal anti-inflammatory drugs(NSAIDs) , selective inhibitors of cyclooxygenase, such as indomethacin, showed a little effect(100μM ; 14%) . (2)Effects on superoxide anion generated by hypoxanthine-xanthine oxidase sys tem (LDH-NADH method) were examined. In this system BW755C most potently inhibited the generation of superoxide anion among these compounds and TZI-41127 and TZI-41078 shoved more potent inhibitions than NSAIDs. (3)TZI-41127, TZI-41078 and BW755C, but not indomethacin and diclofenac-Na, showed potent inhibitory effects on lipid peroxidation in CCl_4 -intoxicated rat liver homogenates . These results suggest that some properties involved in lipoxygenase inhibition participate in scavenging a superoxide anion. TZI-41078 has clinical advantage in reducing lenkocyte-mediated responses in inflammation.