In vitro effect of N-methoxy-3-(3,5-ditert-butyl-4-hydroxybenzylidene)-2-pyrrolidone (E-5110), a novel nonsteroidal anti-inflammatory agent, on generation of some inflammatory mediators
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Cultured rat synovial cells generate PGE2 upon stimulation with a factor derived from rate polymorphonuclear cells (Prostaglandins27, 697, 1984). E-5110 inhibited PGE2 generation by the synovial cells. The IC50 values (μM) for inhibition of PGE2 generation were 0.026 for E-5110, 0.008 for indomethacin, 0.112 for piroxicam, 0.003 for R-830, 0.667 for BW-755C and 2.05 for benoxaprofen. Calcium ionophore A-23187-stimulated LTB4 generation by human neutrophils was inhibited by E-5110 with an IC50 value of 0.20 μM, which was similar to NDGA. The inhibition of LTB4 by E-5110 was more potent than that of R-830, BW-755C or benoxaprofen. E-5110 also inhibited superoxide generation by human neutrophils stimulated with opsonized zymosan, f-Met-Leu-Phe and phorbol myristate acetate. These results indicate that E-5110 is a potent dual inhibitor that suppresses superoxide generation.
KeywordsIndomethacin PGE2 Piroxicam Human Neutrophil Myristate
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