Effects of antioxidant vitamin supplements on Helicobacter pylori-induced gastritis in Mongolian gerbils

BACKGROUND: Epidemiological studies show that high intake of food-bound vitamin C and E reduces the risk of gastric cancer. Whether dietary supplementation with antioxidant micronutrients interferes with Helicobacter pylori infection and associated diseases is unclear. The aim of this study was to investigate if dietary vitamin C or E supplementation influences the progression of gastritis, gastric mucosal nitrosative and oxidative protein damage, gastric mucosal lipid peroxidation, or gastric mucosal oxidative DNA damage in H. pylori-infected Mongolian gerbils. MATERIALS AND METHODS: Gerbils were divided into four groups: H. pylori-infected animals fed with vitamin C- or vitamin E-supplemented food, and infected and uninfected animals given standard rodent food. Subgroups of animals were killed at different time-points until 52 weeks postinfection. Concentrations of 3-nitrotyrosine and thiobarbituric acid-reactive substances (TBARS) in the gastric mucosa were determined with an immunodot blot and a fluorometric method, respectively. Mucosal concentrations of carbonyl carbons on proteins and 8-hydroxydeoxyguanosine were determined by enzyme-linked immunosorbent assay. Gastritis was scored semiquantitatively. RESULTS: Vitamin supplements had no effect on the colonization with H. pylori. Vitamin C as well as vitamin E supplements reduced mucosal 3-nitrotyrosine concentrations to normal levels in infected animals. Vitamin E supplements decreased mucosal protein carbonyls and TBARS in short-term gastritis. In addition, vitamin C supplements caused attenuated mucosal oxidative DNA damage and milder mucosal inflammation in short-term gastritis. CONCLUSION: Vitamin C or vitamin E supplementation leads to some short-term protective effects on H. pylori-induced gastritis in Mongolian gerbils. These effects seem to subside over time when the infection persists.     

Suppression of Helicobacter pylori-induced gastritis by green tea extract in Mongolian gerbils

Since urease of Helicobacter pylori is essential for its colonization, we focused attention on foodstuffs which inhibit the activity of this enzyme. Among plant-derived 77 foodstuff samples tested, some tea and rosemary extracts were found to clearly inhibit H. pylori urease in vitro. In particular, green tea extract (GTE) showed the strongest inhibition of H. pylori urease, with an IC(50) value of 13 microg/ml. Active principles were identified to be catechins, the hydroxyl group of 5(')-position appearing important for urease inhibition. Furthermore, when H. pylori-inoculated Mongolian gerbils were given GTE in drinking water at the concentrations of 500, 1000, and 2000 ppm for 6 weeks, gastritis and the prevalence of H. pylori-infected animals were suppressed in a dose-dependent manner. Since the acquisition by H. pylori of resistance to antibiotics has become a serious problem, tea and tea catechins may be very safe resources to control H. pylori-associated gastroduodenal diseases.     

Effects of aspirin on the development of Helicobacter pylori-induced gastric inflammation and heterotopic proliferative glands in Mongolian gerbils

Background: Helicobacter pylori infection is a major cause of gastritis and gastric carcinoma. Aspirin has anti‐inflammatory and antineoplastic activity. The aim of the present study was to determine the effects of aspirin on H. pylori‐induced gastritis and the development of heterotopic proliferative glands. Methods: H. pylori strain SS1 was inoculated into the stomachs of Mongolian gerbils. Two weeks after inoculation, the animals were fed with the powder diets containing 0 p.p.m. (n = 10), 150 p.p.m. (n = 10), or 500 p.p.m. (n = 10) aspirin. Mongolian gerbils were killed after 36 weeks of infection. Uninfected Mongolian gerbils (n = 10) were used as controls. Histologic changes, epithelial cell proliferation and apoptosis, and prostaglandin E₂ (PGE₂) levels of gastric tissue were determined. Results: H. pylori infection induced gastric inflammation. Administration of aspirin did not change H. pylori‐induced gastritis, but alleviated H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Administration of aspirin accelerated H. pylori‐associated apoptosis but decreased H. pylori‐associated cell proliferation. In addition, the increased gastric PGE₂ levels due to H. pylori infection were suppressed by treatment with aspirin, especially at the dose of 500 p.p.m. Conclusions: Aspirin alleviates H. pylori‐induced hyperplasia and the development of heterotopic proliferative glands. Moreover, aspirin increases H. pylori‐induced apoptosis. We demonstrated the antineoplastic activities of aspirin in H. pylori‐related gastric carcinogenesis.     

Effects of selective cyclooxygenase-2 inhibitor and non-selective NSAIDs on Helicobacter pylori-induced gastritis in Mongolian gerbils

Background. It is still a point of controversy whether Helicobacter pylori‐infected patients are more likely to develop mucosal damage while taking NSADIs. Selective cyclooxygenase (COX‐2) inhibitors may be associated with less severe gastric mucosal damage than conventional NSAIDs, but this association is undefined in H. pylori‐induced gastritis. The aim of this study was to evaluate the effects of selective COX‐2 and nonselective NSAIDs on H. pylori‐induced gastritis. Methods. After intragastric administration of indomethacin, NS‐398 or vehicle alone, once daily for 5 days in H. pylori‐infected and uninfected Mongolian gerbils, we evaluated gastric mucosal damage, inflammatory cell infiltration and prostaglandin E₂ (PGE₂) concentration. We investigated whether H. pylori infection induced the COX‐2 expression. Results. In H. pylori‐uninfected groups, the indomethacin‐treated group showed the highest mucosal damage score and the lowest PGE₂ concentration. There was no difference in mucosal damage scores and PGE₂ concentration between NS‐398 and vehicle‐alone treated group. In H. pylori‐infected groups, there was no difference in mucosal damage scores, irrespective of the type of drugs administered. The indomethacin‐treated group showed the lowest PGE₂ concentration, similar to that of the NS‐398 and vehicle‐alone treated groups, both without H. pylori infection. Gastric neutrophil and monocyte infiltration scores were higher in H. pylori‐infected groups than in uninfected groups. However, there was no difference in these scores according to the type of drugs administered, within H. pylori‐infected or uninfected groups. COX‐2 protein expression was observed in H. pylori‐infected Mongolian gerbils but not in uninfected ones. Conclusions. Our animal study showed that H. pylori infection induced COX‐2 expression and increased prostaglandin concentration. Administration of NSAIDs decreased the prostaglandin concentration, but did not increase mucosal damage in H. pylori‐induced gastritis. Selective COX‐2 inhibitors, instead of conventional NSIADs, had no beneficial effect on preventing mucosal damage in H. pylori‐induced gastritis.     

Effects of estradiol and progesterone on gastric mucosal response to early Helicobacter pylori infection in female gerbils

BACKGROUND: Gender differences have been shown regarding the changes in the inflammatory response, gastrin secretion, and gastric acidity during Helicobacter pylori infection. Aim: To investigate the role of estradiol and progesterone in the changes of the gastric mucosa induced by H. pylori during the early stage of infection in female gerbils. MATERIALS AND METHODS: Thirty-three adult ovariectomized female gerbils were infected with H. pylori (SS1); 7 days after infection they were treated with low and high doses of estradiol (50 and 250 microg/60 days pellet), progesterone (15 and 50 mg/60 days pellet) and vehicle. Non-ovariectomized infected gerbils were used as control. Gerbils were euthanized after 6 weeks of infection. Histologic evaluation, immunohistochemical detection of proliferation cell nuclear antigen (PCNA), gastrin, and apoptosis by terminal deoxynucleotide nick end labeling (TUNEL) assay were performed. Positive cells for PCNA, TUNEL, and gastrin were counted in 10 oriented glands per animal. Two-sided p = .05 was considered significant. RESULTS: Estradiol-treated groups showed more intense and extended acute and follicular gastritis compared to the vehicle group, whereas progesterone-treated groups presented less gastritis than the other groups. Proliferation and apoptosis indexes were significantly lower in the vehicle group when compared with those of the control; both indexes were increased in the high-dose estradiol and progesterone groups as compared with those of the vehicle. Grade I nonmetaplastic atrophy was observed in the vehicle and progesterone groups. The high-dose progesterone group showed a significant reduction in the number of gastrin cells. CONCLUSIONS: Estradiol and progesterone participate in the gastric mucosal response to early H. pylori infection in gerbils.     

高盐溶液预处理幽门螺杆菌对蒙古沙土鼠胃黏膜损伤作用

目的 探讨高盐预处理的幽门螺杆菌(H.pylori)对胃黏膜的损伤作用。 方法 将30%高盐预处理前后的胃癌来源的H.pylori菌株(4854)灌胃蒙古沙土鼠(MGs),在灌胃后13、26和73周解剖动物,通过组织病理学检查、免疫组化染色和黏膜厚度测量,探讨高盐预处理的H.pylori对胃黏膜的损伤作用。 结果 与未加盐预处理的相应菌株相比,高盐预处理组小鼠的慢性炎症、黏膜变性/坏死、腺体萎缩伴肠上皮化生的发生率较低,黏膜糜烂/溃疡和黏膜上皮增生的发生率较高,差异均有统计学意义(t=8.325 6,P=0.040 8)。第73周,高盐预处理4854菌株组胃体和胃窦黏膜增生显著高于未加盐预处理组(t=12.802 4,P=0.035 1;t=16.536 0,P=0.043 8)。 结论 高盐预处理改变了H.pylori的体内致病性,有助于阐明H.pylori感染与高盐饮食在胃病中的相互作用模式。     

Eradication of Helicobacter pylori and resolution of gastritis in the gastric mucosa of IL-10-deficient mice

BACKGROUND: Helicobacter pylori has been shown to induce pronounced gastric inflammation in the absence of interleukin-10 (IL-10) by 6 weeks post inoculation. The ability of IL-10(-/-) mice to eradicate H. pylori has not been demonstrated, possibly due to early sacrifice. Therefore, the long-term effect of enhanced gastritis on H. pylori colonization was determined in IL-10(-/-) mice. METHODS: C57BL/6 and IL-10(-/-) mice were infected with H. pylori and assessed for the degree of gastritis, bacterial load, and in vitro T-cell recall response at 4 and 16 weeks of infection. RESULTS: Infection of IL-10(-/-) mice resulted in significantly more severe gastritis than wild-type control mice and eradication of H. pylori by 4 weeks post inoculation. By 16 weeks, the level of gastritis in IL-10(-/-) was reduced to the levels observed in wild-type mice. Splenocytes from IL-10(-/-) mice were prone to produce significantly greater amounts of IFN-gamma than wild-type mice when stimulated with bacterial antigens. CONCLUSIONS: These results indicate that the host is capable of spontaneously eradicating H. pylori from the gastric mucosa when inflammation is elevated beyond the chronic inflammation induced in wild-type mice, and that the gastritis dissipates following bacterial eradication. Additionally, these data provide support for a model of gastrointestinal immunity in which naturally occurring IL-10-producing regulatory T cells modulate the host response to gastrointestinal bacteria.     

Gastric mucosal cytokine responses in Helicobacter pylori-infected patients with gastritis and peptic ulcers. Association with inflammatory parameters and bacteria load

Helicobacter pylori is an important pathogen in gastroduodenal inflammation and ulceration. Several mechanisms have been proposed to explain its role. We studied the cytokine production patterns in situ in gastric mucosal biopsies from H. pylori-positive and H. pylori-negative patients with dyspepsia. Immunohistochemistry with monoclonal antibodies was used. The study showed enhanced expression of interleukin (IL) -8, IL-10 and interferon-gamma (IFN-gamma) in H. pylori infection and a significant association was found between these cytokines and the following parameters: bacteria load, chronic inflammation and activity. These parameters were significantly correlated with the cell markers CD19 and CD56. The study indicates a dual effect of H. pylori on the Th1 response, i.e. a stimulation of the response verified by increased IFN-gamma and a feed-back verified by an increase of the counterinflammatory IL-10, which may dampen the inflammatory and cytotoxic effect of the Th1 response. Furthermore, the study confirms the connection between increase of IL-8 and inflammatory activity in gastric mucosa in H. pylori infection.     

Effect of probiotics and triple eradication therapy on the cyclooxygenase (COX)-2 expression, apoptosis, and functional gastric mucosal impairment in Helicobacter pylori-infected Mongolian gerbils

BACKGROUND: Helicobacter pylori infection in Mongolian gerbils is an established experimental model of gastric carcinogenesis that mimics H. pylori-positive patients developing gastric ulcer and gastric cancer, but the effect of probiotic therapy on functional aspects of this infection remains unknown. METHODS: We compared the effects of intragastric inoculation of gerbils with H. pylori strain (cagA+ vacA+, 5 x 10(6) colony forming units/ml) with or without triple therapy including omeprazole, amoxicillin, and tinidazol or probiotic bacteria Lacidofil. Histology of glandular mucosa, the viable H. pylori, and density of H. pylori colonization were evaluated. The gastric blood flow was measured by H2-gas clearance method; the plasma gastrin and gastric luminal somatostatin were determined by RIA and expression of cyclooxygenase (COX)-2 and apoptotic Bax and Bcl-2 proteins were evaluated by Western blot. RESULTS: The gastric H. pylori infection was detected in all animals by histology and H. pylori culture. Basal gastric acid was significantly reduced in H. pylori-infected animals but not in those with triple therapy or Lacidofil. Early lesions were seen already 4 weeks upon H. pylori inoculation and consisted of chronic gastritis and glandular atypia associated with typical regenerative hyperplasia and increased mitotic activity and formation of apoptotic bodies. The H. pylori infection was accompanied by the fall in gastric blood flow, the marked increase in plasma gastrin, the significant fall in gastric somatostatin levels and Bcl-2 protein expression, and the rise in expression of COX-2 and Bax proteins. These mucosal changes were counteracted by the triple therapy and Lacidofil. CONCLUSIONS: H. pylori infection in gerbils, associated with regenerative hyperplasia of glandular structure, results in the suppression of gastric secretion, overexpression of COX-2, and enhancement in apoptosis and impairment of both, gastric blood flow and gastrin-somatostatin link that were reversed by anti-H. pylori triple therapy and attenuated by probiotics.     

Teprenone, but not H2-receptor blocker or sucralfate, suppresses corpus Helicobacter pylori colonization and gastritis in humans: teprenone inhibition of H. pylori-induced interleukin-8 in MKN28 gastric epithelial cell lines

Background. The role of teprenone in Helicobacter pylori‐associated gastritis has yet to be determined. To investigate the effect of teprenone on inflammatory cell infiltration, and on H. pylori colonization of the gastric mucosa in H. pylori‐infected patients, we first compared the effect of teprenone with that of both histamine H2 receptor antagonists (H2‐RA) and sucralfate on the histological scores of H. pylori gastritis. We then examined its in vitro effect on H. pylori‐induced interleukin (IL)‐8 production in MKN28 gastric epithelial cells. Materials and Methods. A total of 68 patients were divided into three groups, each group undergoing a 3‐month treatment with either teprenone (150 mg/day), H2‐RA (nizatidine, 300 mg/day), or sucralfate (3 g/day). All subjects underwent endoscopic examination of the stomach before and after treatment. IL‐8 production in MKN28 gastric epithelial cells was measured by enzyme‐linked immunosorbent assay (ELISA). Results. Following treatment, the teprenone group showed a significant decrease in both neutrophil infiltration and H. pylori density of the corpus (before vs. after: 2.49 ± 0.22 vs. 2.15 ± 0.23, p = .009; 2.36 ± 0.25 vs. 2.00 ± 0.24, p = .035, respectively), with no significant differences seen in either the sucralfate or H2‐RA groups. Teprenone inhibited H. pylori‐enhanced IL‐8 production in MKN28 gastric epithelial cells in vitro, in a dose‐dependent manner. Conclusions. Teprenone may modify corpus H. pylori‐associated gastritis through its effect on neutrophil infiltration and H. pylori density, in part by its inhibition of IL‐8 production in the gastric mucosa.