Effects of the nonsteroidal anti-inflammatory compounds Lonazolac Ca, indomethacin and NDGA on inflammatory mediator generation and release from various cells.
The effects of Lonazolac calcium in modulating histamine release, leukotriene and 12-HETE generation and PAF metabolism from various cells were compared with the cyclooxygenase and lipoxygenase inhibitors indomethacin and nordihydroguaiaretic acid (NDGA). For histamine release cells were stimulated with Ca ionophore, A23187. The release of histamine from human basophils was significantly decreased after preincubation of the cells with Lonazolac Ca. Lonazolac Ca and NDGA were equally potent and their activity exceeded that of indomethacin. Preincubation of human polymorphonuclear leukocytes (PMN) with Lonazolac Ca, indomethacin and NDGA at high concentrations led to an inhibition of leukotriene generation induced by either the Ca ionophore or opsonized zymosan. Different concentrations were required for inhibiting the enzymatic and the non-enzymatically generated leukotrienes. Lonazolac Ca was more potent than indomethacin. Incubation of PMN with Lonazolac calcium modulated the metabolism of exogenously added 3H-PAF and 3H-lyso-PAF. In comparison with NDGA. Lonazolac Ca affected different enzymes of the PAF metabolism.
Raulf
M
M
Lehrstuhl Med. Mikrobiologie und Immunologie, Ruhr-Universität Bochum, F.R.G.
König
W
W
D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D001773:Blood Cells / Q000187:drug effects* / Q000378:metabolism; D006636:Histamine Release / Q000187:drug effects; D006801:Humans; D006893:Hydroxyeicosatetraenoic Acids / Q000096:biosynthesis; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D007249:Inflammation / Q000209:etiology* / Q000503:physiopathology; D015289:Leukotrienes / Q000096:biosynthesis; D009637:Masoprocol / Q000494:pharmacology; D010972:Platelet Activating Factor / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology
D000894:Anti-Inflammatory Agents, Non-Steroidal; D006893:Hydroxyeicosatetraenoic Acids; D015289:Leukotrienes; D010972:Platelet Activating Factor; D011720:Pyrazoles; C017472:lonazolac; D019377:12-Hydroxy-5,8,10,14-eicosatetraenoic Acid; D009637:Masoprocol; D007213:Indomethacin