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 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.
Mannick
E E
EE
Department of Pediatrics, Stanley Scott Cancer Center, Louisiana State University Medical Center, New Orleans, Louisiana 70112, USA.
Bravo
L E
LE
Zarama
G
G
Realpe
J L
JL
Zhang
X J
XJ
Ruiz
B
B
Fontham
E T
ET
Mera
R
R
Miller
M J
MJ
Correa
P
P
D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D017209:Apoptosis; D015415:Biomarkers; D001706:Biopsy; D005756:Gastritis / Q000378:metabolism*; D016481:Helicobacter Infections / Q000188:drug therapy / Q000378:metabolism*; D016480:Helicobacter pylori; D006801:Humans; D007124:Immunoenzyme Techniques; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D014443:Tyrosine / Q000031:analogs & derivatives*
D000900:Anti-Bacterial Agents; D015415:Biomarkers; D014443:Tyrosine; D019001:Nitric Oxide Synthase