NO-flurbiprofen maintains duodenal blood flow, enhances mucus secretion contributing to lower mucosal injury.
This study investigates possible mechanisms behind the reduced gastrointestinal ulcerogenicity of nitric oxide (NO)-flurbiprofen compared with flurbiprofen. The duodenal mucosa of Inactin-anaesthetised rats was exteriorized for intravital microscopy. Blood flow was measured with laser-Doppler flowmetry (LDF), mucus thickness with micropipettes, ICAM-1 and P-selectin expression with dual-labeled antibody technique, and mucosal integrity by (51)Cr-EDTA permeability. Exposure of the duodenum to flurbiprofen (1.0 mg/ml) for 90 min significantly reduced LDF to 70 +/- 4%, whereas NO-flurbiprofen (1.3 mg/ml) had no significant effect. Mucus accumulation after 60-min exposure was 75 +/- 23 microm (control), -1 +/- 17 microm (flurbiprofen), and 104 +/- 35 microm (NO-flurbiprofen). Mucosal permeability to (51)Cr-EDTA was unchanged in the control and NO-flurbiprofen groups but increased significantly from 1.0 +/- 0.2 to 3.7 +/- 0.7 microl x min(-1) x g(-1) after 90-min exposure to flurbiprofen. Expression of ICAM-1 was significantly increased after oral flurbiprofen but not by NO-flurbiprofen. Positive effects of NO-flurbiprofen compared with flurbiprofen on mucus formation, blood flow, and adhesion molecule expression likely contribute to the reduced mucosal injury observed with NO-flurbiprofen.
Holm
L
L
Department of Medical Cell Biology, Biomedical Center, Uppsala University, 751 23 Uppsala, Sweden. Lena.Holm@medcellbiol.uu.se
Phillipson
M
M
Perry
M A
MA
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology*; D004338:Drug Combinations; D004386:Duodenum / Q000098:blood supply*; D005480:Flurbiprofen / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D009093:Mucus / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004338:Drug Combinations; D014665:Vasodilator Agents; D009569:Nitric Oxide; D005480:Flurbiprofen