INDUCIBLE NITRIC-OXIDE SYNTHASE, NITROTYROSINE, AND APOPTOSIS IN HELICOBACTER-PYLORI GASTRITIS - EFFECT OF ANTIBIOTICS AND ANTIOXIDANTS

Helicobacter pylori infection is a known risk factor for gastric cance r, We hypothesized that H. pylori infection would lead to the sustaine d production of the reactive nitrogen species nitric oxide and peroxyn itrite as part of the host immune response, We further hypothesized th at H. pylori infection would lead to increased apoptosis of gastric ep ithelial cells, possibly in response to free radical-mediated DNA dama ge, Using immunohistochemistry, we stained and scored gastric antral b iopsies from 84 Colombian patients with nonatrophic gastritis before a nd after treatment for H. pylori infection, We examined expression of inducible nitric oxide synthase (iNOS); nitrotyrosine, a marker for pe roxynitrite; and DNA fragmentation, a marker for apoptosis, Patients w ere treated with triple therapy (amoxicillin, 500 mg three times a day for 2 weeks; metronidazole, 400 mg three times a day for 2 weeks; and bismuth subsalicylate, 262 mg four times a day for 2 weeks, followed by 262 mg every day for 4-12 months), Eradication of H. pylori infecti on resulted in a significant reduction in iNOS and nitrotyrosine stain ing and a marginally significant reduction in apoptosis. Dietary suppl ementation with beta-carotene (30 mg every day for 4-12 months) result ed in a significant decrease in iNOS staining, Supplementation with as corbic acid (1 g twice a day for 4-12 months) led to a significant red uction in nitrotyrosine staining, In patients supplemented with either ascorbic acid or beta-carotene, there was a trend toward a reduction in apoptosis, but this was not statistically significant, We conclude that H. pylori infection is accompanied by the formation of endogenous reactive nitrogen intermediates, which may contribute to DNA damage a nd apoptosis, In addition to antimicrobial therapy, dietary supplement ation with beta-carotene and ascorbic acid may prevent the formation o f these potential carcinogens.