Role of Free Radical Scavengers in the Management of Refractory Duodenal Ulceration: A New Approach

Abstract

This prospective randomized double blind study examined the influence of free radical scavengers on the healing and recurrence of refractory duodenal ulceration. To this end, allopurinol (50 mg, four times a day) —a hydroxyl radical scavenger and an inhibitor of xanthine oxidase, the enzyme which forms superoxide radicals—and dimethyl sulfoxide (DMSO, 500 mg, four times a day)—a hydroxyl radical scavenger—were administered orally. Three hundred and sixty-three consecutive patients with duodenal ulceration that did not heal despite 3 months of treatment with cimetidine, who were cigarette smokers and social drinkers, were randomized to receive 800 mg cimetidine twice a day alone or with either allopurinol or DMSO. In 315 patients who were evaluable for efficacy analysis, the healing rate at 8 weeks was, for cimetidine alone, 60%; for cimetidine with DMSO, 100%; and for cimetidine with allopurinol, 100%. The healing efficacy of cimetidine was therefore significantly ( P < 0.01) heightened by DMSO and allopurinol. The patients whose ulcers healed were instituted on maintenance treatment for 1 year and received 800 mg cimetidine at bedtime alone or with either DMSO or allopurinol. In 218 patients who were evaluable for efficacy analysis, the cumulative relapse rate at 1 year was, for cimetidine alone, 29%; for cimetidine with DMSO, 8%; and for cimetidine with allopurinol, 7%. DMSO with cimetidine and allopurinol with cimetidine were, therefore, superior to cimetidine alone ( P < 0.01) in preventing ulcer relapse. The results suggest that oxygen-derived free radicals are implicated in the mechanism of refractory duodenal ulceration and that scavenging these radicals stimulates healing and reduces recurrence of the ulceration.