Abstract
There have been increasing findings indicating that free radicals and microcirculatory disturbances in gastric mucosa play an important role in the mucosal injury induced by non-steroidal antiinflammatory drugs, besides the inhibitory effect of these drugs on prostaglandin production. Therefore, we evaluated the effect of ampiroxicam, a prodrug of piroxicam, on the levels of reduced glutathione (GSH) in rat gastric mucosa and the mucosal microcirculation in rats by using a technique of intravitalmicroscopy. GSH levels were examined 5 hr after the oral administration of ampiroxicam, piroxicam and indomethacin. Ampiroxicam (13.5 mg/kg) caused a significant decrease of the gastric mucosal GSH content, however, this effect was apparently weaker than those of piroxicam (10 mg/kg) and indomethacin (12.5 mg/kg) . In observation of the basal part of the mucosal microcirculation by intravitalmicroscopy, local application of ampiroxicam (0.2 mM) on gastric submucosa had little or no effect on the diameter of collecting venules in the mucosa. On the other hand, a similar application of piroxicam or indomethacin produced a long-lasting constriction of the venules.
These results suggest that a weak effect of ampiroxicam on the microcirculation system in gastric mucosa may be one explanation of the ameliorated ulcerogenic activity of this drug.
