Role of Vascular Mechanisms Involved in the Acute Gastric Mucosal Injury Induced by Droxicam and Piroxicam in Rats

Abstract

We describe the formation of severe gastric erosions produced in fasted rats by intragastric administration of droxicam and its active species piroxicam, non-steroidal anti-inflammatory drugs of the oxicam group. The time course of gastric damage and the possible role of mucus secretion, changes of gastric vascular permeability, and neutrophil activation in the development of droxicam- and piroxicam-induced gastric lesions, were also investigated. Both drugs dose-dependently (1.25-20 mg kg−1) caused acute gastric haemorrhagic erosions in the rat. These lesions were significantly greater with piroxicam treatment 6 h after dosing. Only the lower doses of droxicam and piroxicam (1.25 mg kg−1) induced a significant increase of mucus gel production at different times (3 and 6 h). However, there was no increase in the concentration of its components. Oral pretreatment of the animals with either agent did not induce any changes on the values of mucosal vascular permeability. In contrast, myeloperoxidase activity as an index of neutrophil infiltration was significantly increased. A marked relationship was found between the lesion index and myeloperoxidase activity. These results suggest that neutrophil infiltration could play an important role in the pathogenesis of gastric mucosal injury induced by these oxicam agents.