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• W2100683477 abstract "The nitric oxide (NO)-donating nitroxybutyl ester of flurbiprofen (NO-flurbiprofen), shows reduced gastro-intestinal toxicity relative to flurbiprofen. NO may exert either pro- or anti-apoptotic effects, while non-steroidal anti-inflammatory drugs may induce apoptosis. The aim of the present work was therefore to compare the effects of flurbiprofen and NO-flurbiprofen on apoptosis in guinea-pig gastric mucous cells. Apoptotic activity was assessed by assay of caspase activity and from the fragmentation and condensation of nuclei. Incubation with flurbiprofen for 24 h produced a concentration-dependent induction of apoptosis in cells attached to the culture plate (caspase 3-like activity increased by 257% at 500 microM), while NO-flurbiprofen inhibited basal apoptosis (caspase 3-like activity decreased by 71% at 500 microM). Caspase activity and nuclear fragmentation were substantially increased in cells that had spontaneously detached from the culture plate. NO-flurbiprofen inhibited caspase activity (55% at 500 microM) but not nuclear fragmentation in these detached cells. NO flurbiprofen inhibited the activation of apoptosis by 25 microM C(6)-ceramide in cells attached to the culture plate. Inhibition of caspase activity by NO-flurbiprofen was detectable after 6 h of incubation with intact cells, but by contrast with the NO-donor S-nitrosyl-N-acetyl-penicillamine, was not demonstrable with cell homogenates. Activation of caspase 3-like activity by flurbiprofen was slow (>6 h incubation needed) and was inhibited by cycloheximide. The presence of a nitroxybutyl ester moiety on flurbiprofen prevents the pro-apoptotic activity of the parent compound and may contribute to the reduced gastro-intestinal toxicity of NO-flurbiprofen." @default.
• W2100683477 created "2016-06-24" @default.
• W2100683477 creator A5052393900 @default.
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• W2100683477 date "2000-06-01" @default.
• W2100683477 modified "2023-09-27" @default.
• W2100683477 title "Opposite effects of flurbiprofen and the nitroxybutyl ester of flurbiprofen on apoptosis in cultured guinea-pig gastric mucous cells" @default.
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• W2100683477 doi "https://doi.org/10.1038/sj.bjp.0703383" @default.
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