EFFECT OF ALLOPURINOL AND SUPEROXIDE-DISMUTASE ON INDOMETHACIN-INDUCED GASTRIC-LESIONS IN THE RAT

Gastric lesions induced by indomethacin (20 mg.kg-1 i.p.) were studied in rats after a 24 hour fast. The size of the lesions was correlated with gastric vascular permeability (determined from the Evans blue con centration in the stomach tissue after its i.v administration) and wit h the rate of gastric emptying (determined from the phenol red concent ration after its intragastric application). These changes were correla ted with the prevention of gastric lesions by allopurinol (50 mg.kg-1) after a single dose or once dally for 3 days before indomethacin and by a single dose (15 000 U.kg-1) of superoxide dismutase (SOD). Indome thacin significantly increases the rate of gastric emptying concomitan tly with gastric vascular permeability. The pretreatment of animals wi th allopurinol and SOD inhibits gastric lesions as well as gastric vas cular permeability without changing gastric emptying which was increas ed after indomethacin administration. The inhibition of gastric lesion formation and gastric vascular permeability was more marked in rats p retreated with allopurinol for 3 days when compared with rats treated with a single dose of allopurinol only. These results support the sugg estion that oxygen-derived free radicals contribute to the pathogenesi s of indomethacin-induced gastric lesions.