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Ketoprofen-induced intestinal permeability changes studied in side-by-side diffusion cells
Legen, Igor ; Kristl, Albin
It is known that non-steroidal anti-inflammatory drugs (NSAIDs) increase intestinal permeability. Increased intestinal permeability is believed to result from the opening of tight junctions because ...of NSAID-induced reduction of prostaglandin synthesis andžor energy-depletion. In this study, ketoprofen-induced changes in intestinal permeability were evaluated by measuring tissue electrical parameters, namely tissue electrical resistance (TER), short circuit current (Isc) and transepithelial potential difference (PD), and the transport of a paracellular marker, fluorescein, across rat jejunum in-vitro. Ketoprofen, added to the mucosal side of the tissue, decreased TER and increased fluorescein transport in a concentration-dependentmanner. Isc values and the active transport of D-glucose were not affected at ketoprofen concentrations of less than 5 mM. Higher ketoprofen concentrations decreased Isc values and diminished active transport of D-glucose, while transport of fluorescein increased markedly. Similar effects on intestinal properties were observed when the metabolic inhibitor sodium azide was added to the incubation medium. The results of thisstudy suggest that the increased intestinal permeability observed at lowerketoprofen concentrations (< 5 mM) is most probably a consequence of reduced prostaglandin tight junction control, whereas at higher concentrations, ATP depletion caused by ketoprofen seems to be the major mechanism for increased intestinal permeability.
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