{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,11,19]],"date-time":"2024-11-19T15:52:58Z","timestamp":1732031578075},"reference-count":33,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2009,1,29]],"date-time":"2009-01-29T00:00:00Z","timestamp":1233187200000},"content-version":"vor","delay-in-days":3164,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2000,6]]},"abstract":"<jats:p>\n<jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The nitric oxide (NO)\u2010donating nitroxybutyl ester of flurbiprofen (NO\u2010flurbiprofen), shows reduced gastro\u2010intestinal toxicity relative to flurbiprofen. NO may exert either pro\u2010 or anti\u2010apoptotic effects, while non\u2010steroidal anti\u2010inflammatory drugs may induce apoptosis. The aim of the present work was therefore to compare the effects of flurbiprofen and NO\u2010flurbiprofen on apoptosis in guinea\u2010pig gastric mucous cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Apoptotic activity was assessed by assay of caspase activity and from the fragmentation and condensation of nuclei.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Incubation with flurbiprofen for 24\u2003h produced a concentration\u2010dependent induction of apoptosis in cells attached to the culture plate (caspase 3\u2010like activity increased by 257% at 500\u2003\u03bc<jats:sc>M<\/jats:sc>), while NO\u2010flurbiprofen inhibited basal apoptosis (caspase 3\u2010like activity decreased by 71% at 500\u2003\u03bc<jats:sc>M<\/jats:sc>).<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Caspase activity and nuclear fragmentation were substantially increased in cells that had spontaneously detached from the culture plate. NO\u2010flurbiprofen inhibited caspase activity (55% at 500\u2003\u03bc<jats:sc>M<\/jats:sc>) but not nuclear fragmentation in these detached cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>NO flurbiprofen inhibited the activation of apoptosis by 25\u2003\u03bc<jats:sc>M<\/jats:sc> C<jats:sub>6<\/jats:sub>\u2010ceramide in cells attached to the culture plate.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibition of caspase activity by NO\u2010flurbiprofen was detectable after 6\u2003h of incubation with intact cells, but by contrast with the NO\u2010donor S\u2010nitrosyl\u2010N\u2010acetyl\u2010penicillamine, was not demonstrable with cell homogenates.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Activation of caspase 3\u2010like activity by flurbiprofen was slow (&gt;6\u2003h incubation needed) and was inhibited by cycloheximide.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The presence of a nitroxybutyl ester moiety on flurbiprofen prevents the pro\u2010apoptotic activity of the parent compound and may contribute to the reduced gastro\u2010intestinal toxicity of NO\u2010flurbiprofen.<\/jats:p><\/jats:list-item>\n<\/jats:list>\n<\/jats:p><jats:p><jats:italic>British Journal of Pharmacology<\/jats:italic> (2000) <jats:bold>130<\/jats:bold>, 811\u2013818; 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