Helicobacter pylori
infection is a known risk factor for
gastric cancer. We hypothesized that H. pylori
infection would lead to the sustained production of the
reactive nitrogen species nitric oxide and
peroxynitrite as part of the host immune response. We further hypothesized that H. pylori
infection would lead to increased apoptosis of gastric epithelial cells, possibly in response to
free radical-mediated DNA damage. Using immunohistochemistry, we stained and scored gastric
antral biopsies from 84 Colombian patients with nonatrophic
gastritis before and
after treatment for H. pylori
infection. We examined expression of
inducible nitric oxide synthase (iNOS);
nitrotyrosine, a marker for
peroxynitrite; and DNA fragmentation, a marker for apoptosis. Patients were 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
infection resulted in a significant reduction in iNOS and
nitrotyrosine staining and a marginally significant reduction in apoptosis. Dietary supplementation with
beta-carotene (30 mg every day for 4-12 months) resulted in a significant decrease in iNOS staining. Supplementation with
ascorbic acid (1 g twice a day for 4-12 months) led to a significant reduction 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 and apoptosis. In addition to antimicrobial
therapy, dietary supplementation with
beta-carotene and
ascorbic acid may prevent the formation of these potential
carcinogens.