REDUCTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUG-INDUCED GASTRIC INJURY AND LEUKOCYTE-ENDOTHELIAL ADHESION BY OCTREOTIDE

Background-Non-steroidal anti-inflammatory drugs (NSAIDs) induce gastr ic ulcers. Aims-To assess whether the somatostatin analogue octreotide prevents NSAID induced mucosal gastrointestinal damage in both animal s and humans. The effect of octreotide on neutrophil adhesion to the e ndothelium was also evaluated. Methods-Male Sprague-Dawley rats were p retreated either with saline (0.3 ml subcutaneously) or octreotide (0. 001-1 ng/kg subcutaneously). After 30 minutes gastric ulcers were indu ced by the intragastric application of NSAIDs (20 mg/kg indomethacin, 200 mg/kg aspirin, 200 mg/kg ibuprofen, or 50 mg/kg diclofenac). Four hours later the rats were killed and gastric mucosal lesions were asse ssed by computed planimetry. To determine whether octreotide could pre vent indomethacin induced injury in humans, 20 healthy volunteers were evaluated in a double blind, placebo controlled study. Results-Octreo tide prevented NSAID induced gastric mucosal lesions (p < 0.05). The d ose response curve was U shaped and the most effective dose was 0.1 ng /kg. Leucocyte adherence in submucosal venules of the stomach was eval uated by in vivo microscopy. Octreotide (0.1 ng/kg subcutaneously) pre vented indomethacin (20 mg/kg intragastric) induced leucocyte adherenc e in gastric submucosal venules (p < 0.05). Healthy human volunteers r eceived 50 mg indomethacin orally thrice a day concomitantly with eith er an identical placebo or 0.01 mu g, 0.1 mu g, or 1 mu g octreotide s ubcutaneously thrice a day for three days. Injury was assessed by endo scopy. There was a negative correlation between the octreotide dose an d injury score (p < 0.03 for gastric injury, p < 0.001 for duodenal in jury). Conclusions-Octreotide protects the stomach from NSAID induced gastric injury, probably via its ability to reduce NSAID induced neutr ophilic adhesion to the microvasculature. Octreotide also ameliorated indomethacin induced gastric and duodenal injury in humans.