Gastric mucosal cytoprotection in the rat by scavenging oxygen-derived free radicals

Oxygen-derived free radicals are cytotoxic and promote tissue damage. Dimethyl sulfoxide (DMSO) and allopurinol scavenge hydroxyl radicals, and the latter agent also inhibits the enzyme xanthine oxidase, which is responsible for the formation of superoxide anions. These agents were given daily by gavage (1 ml/d). After 2 days of administration as 1, 2, or 5% solutions, the H+ output of the rat with or without pyloric ligation was not significantly affected. After six hours reserpine (5 mg/kg i.p.) or serotonin (50 mg/kg i.p.) produced ischemic mucosal injury in all stomachs (39 +/- 5.2 mm2 and 25.9 +/- 2.8 mm2, mean +/- standard error of the mean [SEM], n = 10). Pretreatment for 2 days with 1 ml/d of 1% allopurinol or DMSO significantly (p less than 0.001) protected the rat against the reserpine (23 +/- 2.1 mm2 and 24 +/- 1.9 mm2, respectively, vs 39 +/- 5.2 mm2, n = 10) and serotonin injury (10 +/- 1.5 mm2 and 11 +/- 1.8 mm2, respectively, vs 25.9 +/- 2.8 mm2, n = 10). However, 2 days pretreatment with 1 ml/d of 2% allopurinol or DMSO was more effective (p less than 0.001) in this respect, and injury only developed in 40% of the rats given reserpine (8 +/- 1.2 mm2 and 9 +/- 1.6 mm2) and in 20% of those given serotonin (2.4 +/- 0.4 mm2 and 1.9 +/- 0.5 mm2). Similar pretreatment with 5% solutions completely protected the rat stomach against the reserpine and serotonin injuries without significantly influencing the H+ output.(ABSTRACT TRUNCATED AT 250 WORDS)