Vitamin E and carotenoids in gastric biopsies: the relation to plasma concentrations in patients with and without Helicobacter pylori gastritis.

The carotenoids--lycopene and alpha- and beta-carotene-- and alpha-tocopherol were measured in plasma and in mucosal biopsies in normal subjects and in those infected with Helicobacter pylori. Two indexes of the presence of the reactive oxygen species malondialdehyde and chemiluminescence were measured in biopsies taken from adjacent sites in the same patient. In general, plasma and mucosal concentrations of all antioxidants correlated well and were of a similar order or magnitude in plasma and mucosa. There was no significant difference between the slope of the regression lines nor an overall difference in the concentrations of these antioxidants between the H. pylori-positive and control groups, indicating an absence of effect of H. pylori infection. However, a marked difference was seen in chemiluminescence and malondialdehyde concentrations in biopsies. For chemiluminescence this was highly significant. These findings confirm the presence of free radicals in the mucosa of H. pylori-infected patients and suggest therefore that the lipid-soluble antioxidants have either no role in protecting mucosal cells from free radical damage or, if they are able to scavenge these species, they are then rapidly regenerated to their original forms by redox and other processes.

Ranitidine in a twice daily triple-therapy regimen for the eradication of Helicobacter pylori.

OBJECTIVE: To compare the efficacy and safety of ranitidine 300 mg twice daily plus amoxycillin 1000 mg twice daily for 2 weeks (RA2) with ranitidine 300 mg twice daily, amoxycillin 1000 mg twice daily, plus tinidazole 500 mg twice daily for 2 weeks (RAT2) for the eradication of Helicobacter pylori. DESIGN: Prospective, randomized, double-blind, parallel-group study in patients who were H. pylori positive on 13C urea breath test (13C UBT). SETTING: Twenty-four UK consultant gastroenterologists entered mostly hospital out-patients. PATIENTS: A total of 232 patients with gastric or duodenal ulceration or endoscopic appearances suggestive of gastritis (160 male, 72 female, mean age 51) were entered following routine endoscopy; 223 were H. pylori positive on 13C UBT. Patients with medical conditions or medications which could interfere with study response or measurements and those at risk of pregnancy were excluded. Two hundred and three patients completed the study. INTERVENTIONS: Patients underwent endoscopy with biopsy for rapid urease (CLO) test. Those who were positive had a 13C UBT. Patients were randomized to receive RA2 or RAT2. Eradication of H. pylori was assessed by 13C UBT 4 weeks after completion of therapy. Blood was taken for haematological and biochemical screening at the beginning and end of treatment. MAIN OUTCOME MEASURE: H. pylori eradication at least 28 days after end of treatment. RESULTS: In the intention-to-treat sample analysis, H. pylori was eradicated in 78/115 patients (68%) taking RAT2 and 42/108 patients (39%) taking RA2. In the per-protocol sample analysis H. pylori eradication was successful in 68/79 patients (86%) taking RAT2 and 36/71 patients (51%) taking RA2. One hundred and seventeen patients experienced 242 adverse events. CONCLUSION: Twice daily ranitidine triple therapy is a useful H. pylori eradication regimen.

Ascorbic acid may protect against human gastric cancer by scavenging mucosal oxygen radicals.

High dietary ascorbic acid intake appears to protect against gastric cancer. This may be due to its action as a scavenger of reactive radical species formed in the gastric mucosa, resulting in a reduced level of radical-mediated DNA damage. We have studied 82 patients, of whom 37 had Helicobacter pylori-associated gastritis, a condition which predisposes to gastric cancer. Using electron paramagnetic resonance (EPR) spectroscopy we have demonstrated, for the first time, that ascorbyl radicals are generated in human gastric mucosa, presumably as a result of scavenging of free radicals by ascorbic acid. Quantification of ascorbyl radicals demonstrates that there is a higher concentration in those patients with H.pylori gastritis compared with subjects with normal histology (P < 0.01). We also found gastric mucosal luminol-enhanced chemiluminescence and malondialdehyde concentrations (which are believed to be markers of radical generation and tissue damage) to be higher in patients with H.pylori gastritis compared with those with normal histology (P < 0.001 and P < 0.01 respectively). The observed concentrations of the ascorbyl radical correlate with the level of luminol-enhanced chemiluminescence (r = 0.41, P < 0.001), but not with malondialdehyde concentrations (r = 0.08, P = 0.47). Mucosal ascorbic acid and total vitamin C concentrations did not vary between histological groups, nor did they correlate with mucosal levels of the ascorbyl radical, chemiluminescence or malondialdehyde. These data suggest that ascorbic acid is acting as a scavenger of free radicals generated in human gastric mucosa. The experiments therefore provide direct supportive evidence for the hypothesis that ascorbic acid protects against gastric cancer by scavenging reactive radical species which would otherwise react with DNA, with resultant genetic damage.

Ascorbic acid and total vitamin C concentrations in plasma, gastric juice, and gastrointestinal mucosa: effects of gastritis and oral supplementation.

Epidemiological evidence suggests that high dietary ascorbic acid reduces gastric cancer risk. It may do this by either reducing N-nitroso compound formation in gastric juice, or by scavenging reactive oxygen species in gastric mucosa. The aim of this study was to discover if potential ascorbic acid protection might be increased by supplementation. Thirty two patients were supplemented with ascorbic acid, 500 mg twice daily for two weeks. Gastric juice, plasma, and upper gastrointestinal biopsy ascorbate concentrations were measured and compared with values in 48 unsupplemented patients. It was found that ascorbic acid and total vitamin C concentrations were considerably higher in biopsy specimens from oesophagus, body, antrum, duodenum, and rectum, compared with values in plasma or gastric juice. Plasma and mucosal concentrations were unaffected by the presence of chronic gastritis but gastric juice concentrations were substantially lower in patients with chronic gastritis than in patients with normal histological assessment (p < 0.01). Patients receiving ascorbic acid supplements had higher ascorbic acid concentrations in plasma (p < 0.001), gastric juice (p < 0.001), and at all biopsy sites in the upper gastrointestinal tract (p < 0.05). Gastric juice ascorbic acid and total vitamin C concentrations in gastritic patients, however, were still less after supplementation than in normal subjects (p < 0.01). These data suggest that high ascorbic acid intake could reduce gastric cancer risk, but its protective effect might be greater if gastritis is treated (for example, by Helicobacter pylori eradication).

Reactive oxygen species activity and lipid peroxidation in Helicobacter pylori associated gastritis: relation to gastric mucosal ascorbic acid concentrations and effect of H pylori eradication.

BACKGROUND: Helicobacter pylori is an independent risk factor for gastric cancer, and this association may be due to the bacterium causing reactive oxygen species mediated damage to DNA in the gastric epithelium. High dietary ascorbic acid intake may protect against gastric cancer by scavenging reactive oxygen species. AIMS: To assess reactive oxygen species activity and damage in gastric mucosa in relation to gastric pathology and mucosal ascorbic acid level, and to determine the effect of H pylori eradication on these parameters. PATIENTS: Gastric biopsy specimens were obtained for analysis from 161 patients undergoing endoscopy for dyspepsia. METHODS: Reactive oxygen species activity and damage was assessed by luminol enhanced chemiluminescence and malondialdehyde equivalent estimation respectively. Ascorbic acid concentrations were measured using HPLC. RESULTS: Chemiluminescence and malondialdehyde levels in gastric mucosa were higher in patients with H pylori gastritis than in those with normal histology. Successful eradication of the bacterium led to decreases in both parameters four weeks after treatment was completed. Gastric mucosal ascorbic acid and total vitamin C concentrations were not related to mucosal histology, but correlated weakly with reactive oxygen species activity (chemiluminescence and malodialdehyde levels). CONCLUSIONS: Data suggest that reactive oxygen species play a pathological role in H pylori gastritis, but mucosal ascorbic acid is not depleted in this condition.

The effect of Helicobacter pylori infection on levels of DNA damage in gastric epithelial cells.

BACKGROUND: Helicobacter pylori infection leads to an increased risk of developing gastric cancer. The mechanism through which this occurs is not known. We aimed to determine the effect of H. pylori and gastritis on levels of DNA damage in gastric epithelial cells. METHODS: Epithelial cells were isolated from antral biopsies from 111 patients. DNA damage was determined using single cell gel electrophoresis and the proportion of cells with damage calculated before and 6 weeks after eradication of H. pylori. Cell suspensions generated by sequential digestions of the same biopsies were assayed to determine the effect of cell position within the gastric pit on DNA damage. RESULTS: DNA damage was significantly higher in normal gastric mucosa than in H. pylori gastritis [median (interquartile range) 65% (58.5-75.8), n = 18 and 21% (11.9-29.8), n = 65, respectively, p <.001]. Intermediate levels were found in reactive gastritis [55.5% (41.3-71.7), n = 13] and H. pylori negative chronic gastritis [50.5% (36.3-60.0), n = 15]. DNA damage rose 6 weeks after successful eradication of H. pylori[to 39.5% (26.3-51.0), p =.007] but was still lower than in normal mucosa. Chronic inflammation was the most important histological factor that determined DNA damage. DNA damage fell with increasing digestion times (r = -.92 and -.88 for normal mucosa and H. pylori gastritis, respectively). CONCLUSIONS: Lower levels of DNA damage in cells isolated from H. pylori infected gastric biopsies may be a reflection of increased cell turnover in H. pylori gastritis. The investigation of mature gastric epithelial cells for DNA damage is unlikely to elucidate the mechanisms underlying gastric carcinogenesis.