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Am J Physiol Gastrointest Liver Physiol (August 14, 2002). doi:10.1152/ajpgi.00480.2001
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Articles in PresS, published online ahead of print August 14, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00480.2001
Submitted on November 12, 2001
Accepted on June 25, 2002

Lack of duodenal injury with NO-flurbiprofen associated with maintained blood flow and enhanced mucus secretion

Lena Holm1*, Mia Phillipson1, and Michael A Perry2

1 Department of Medical Cell Biology, Division of Physiology, Uppsala University, Uppsala, Sweden
2 Department of Pharmacology and Physiology, University of New South Wales, Sydney, New South Wales, Australia

* To whom correspondence should be addressed. E-mail: lena.holm{at}medcellbiol.uu.se.

This study investigates possible mechanisms behind the reduced gastrointestinal ulcerogenicity of NO-flurbiprofen compared to 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 51Cr-EDTA permeability. Exposure of the duodenum to flurbiprofen (1.0 mg.ml-1) for 90 min significantly reduced LDF to 70±4% while NO- flurbiprofen (1.3 mg.ml-1) had no significant effect. Mucus accumulation, after 60 min exposure was 75±23 µm (control), -1±17 µm (flurbiprofen) and 104±35 µm (NO- flurbiprofen). Mucosal permeability to 51Cr-EDTA was unchanged in the control and NO- flurbiprofen groups but increased significantly from 1.0±0.2 µl.min-1.g-1 to 3.7±0.7 µl.min-1.g-1 after 90 min exposure to flurbiprofen. Expression of ICAM-1 was significantly increased following oral flurbiprofen, but not by NO-flurbiprofen. The positive effects of NO-flurbiprofen compared to flurbiprofen, on mucus formation, blood flow and adhesion molecule expresion likely contribute to the reduced mucosal injury observed with NO-flurbiprofen.




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