The relation between gastric vitamin C concentrations, mucosal histology, and CagA seropositivity in the human stomach

Abstract

Background-Vitamin C may be protective against gastric cancer though infection with Helicobacter pylori is associated with a reduction in intragastric concentrations of vitamin C. Aims-To examine the eVects of H pylori infection, gastric juice pH, the severity and extent of gastric inflammation, and CagA antibody status of the individual on gastric juice and mucosal vitamin C concentrations. Patients-One hundred and fifteen patients undergoing routine gastroscopy for investigation of dyspepsia. Methods-High performance liquid chromatography was used to determine vitamin C concentrations. CagA antibody was detected by western blot analysis. Results-Gastric juice ascorbic acid concentration was significantly lower in patients infected with H pylori compared with those uninfected (19.3 µmol/l (interquartile range (IQR) 10.7-44.5) versus 66.9 µmol/l (IQR 24.4-94.2), p=0.003). The reduction in gastric juice ascorbic acid concentration was inversely related to the severity of gastritis (p=0.01). CagA positive patients had significantly lower gastric juice ascorbic acid concentrations than CagA negative ones (14.8 µmol/l (IQR 7.9-52.2) versus 39 µmol/l (IQR 19.9-142.2), p=0.05). Decreased gastric juice dehydroascorbic acid concentrations were observed in patients with gastric atrophy and intestinal metaplasia. Mucosal ascorbic acid concentrations were also significantly lower in infected patients than uninfected patients (p=0.04). Conclusions-The reduction in gastric vitamin C concentrations is related to gastric juice pH, the severity and extent of gastritis, the presence of H pylori, and the CagA antibody status of the individual. These findings may have implications in H pylori associated carcinogenesis. (Gut 1998;43:322-326)

Molecular mechanisms ofH. pyloriassociated gastric carcinogenesis

“…Increased cell proliferation in the absence of a corresponding increase in apoptosis may explain the increased gastric cancer risk associated with infection by CagA + strains [10] . protein is carcinogenic, the enhanced inflammation and marked reduction of gastric juice vitamin C levels in CagA + strain infected patients may ply a role in H. pylori associated carcinogenesis [16] . H. pylori expresses a powerful urease enzyme, which catalyses the conversion of urea to ammonia.…”

“…A series of studies have demonstrated that concentrations of ammonia comparable to those found in gastric juice of infected individuals can cause gastric atrophy in rats, increase epithelial cell proliferation, and act as a promoter in the methyl-N' nitro-Nnitrosoguanidine (MNNG) rat model of gastric cancer [23][24][25][26][27][28] . Furthermore, H. pylori phospholipases, proteases and oxidases have been shown to cause degradation of many molecules, such as phospholipids in bio-membranes, transforming growth factor-β (TGF-β) and vitamin C, which are important in preventing carcinogenesis [16,[29][30][31] .…”

“…Our in vitro studies showed that the a bove vitamins can also significantly inhibit gastric cancer cell proliferation and induce apoptosis [15] .Investigations on gastric vitamins in patients with and without H. pylori infection suggest that H. pylori infection affects the concentrations of vitamin C, E and β-carotene in the stomach and the CagA + strains have an even greater ability to reduce gastr ic juice vitamin C levels [16,17] . Although many factors may be related to H. pylori associated gastric carcinogenesis, the underlying molecular mechanisms are still unknown.…”

The Decreasing Burden of Gastric Cancer in Japan

“…Since H. pylori was discovered (Warren and Marshall 1983) and its pathogenesis was reported (Marshall et al 1985), many researchers have taken notice of various factors associated with the development of this disease, especially carcinogenesis, and have conducted many biological studies (Anti et al 1998;Honda et al 1998;Sugiyama et al 1998;Watanabe et al 1998;Zhang et al 1998;El-Omar et al 2000;Peek et al 2000;Wang et al 2000). At the same time, many epidemiological studies have been published in the international literature.…”

Possible Reactions of Dietary Phenolic Compounds with Salivary Nitrite and Thiocyanate in the Stomach

“…This is deduced from the results that nitrous acid-induced oxidation of quercetin and chlorogenic acid is inhibited by ascorbic acid [37,38] and the inhibition accompanies the formation of monodehysroascorbic acid radical [38]. The ascorbic acid-dependent inhibition of their oxidation suggests that ascorbic acid in gastric juice, the concentration of which ranges from 0 to 0.5 mM (average, about 0.1 mM) [39][40][41], can suppress the nitrous acid-induced oxidation of phenolic compounds in the stomach. These results suggest that efficiency of the transport of phenolic compounds, which can react with nitrous acid readily, to the intestine is dependent on the concentrations of both salivary nitrite and gastric ascorbic acid.…”