Pylori-induced Gastric Damage Research Articles

Anti-inflammatory and anti-oxidative effect of Korean propolis on Helicobacter pylori-induced gastric damage in vitro.

Helicobacter pylori, present in the stomach lining, is a Gramnegative bacterium that causes various gastrointestinal diseases, including gastritis and peptic ulcers. Propolis is a natural resinous substance collected from a variety of plants, and contains several natural bioactive substances. The aim of this study was to investigate the anti-inflammatory and antioxidative effects of Korean propolis on H. pylori-induced damage in the human adenocarcinoma gastric cell line. The propolis used in this study was obtained from the Korea Beekeeping Association in South Korea. The expression of pro-inflammatory interleukins (ILs), such as IL-8, IL-12, IL-1β, tumor necrosis factor alpha, cyclooxygenase-2, and inducible nitric oxide synthase, which was increased after H. pylori infection, significantly decreased in a dose-dependent manner upon pretreatment with Korean propolis, because of the suppression of mitogen-activated protein kinases and nuclear factor kB pathway. The anti-oxidative activity of propolis was assessed using the 2,2-diphenyl-1-picrylhydrazyl hydrate free radical assay. Korean propolis showed significant anti-oxidative effects via reactive oxygen species scavenging. In addition, pretreatment with Korean propolis upregulated the expression of anti-oxidant enzymes through Nrf2 signaling activation. These findings indicate that the use of Korean propolis, which has anti-inflammatory and anti-oxidative effects, can be promising for the prevention of H. pylori-induced gastric damage.

Controlled, Household-Randomized, Open-Label Trial of the Effect of Treatment ofHelicobacter pyloriInfection on Iron Deficiency among Children in Rural Alaska: Results at 40 Months

Helicobacter pylori infection treatment was found not to reduce the prevalence of iron deficiency or anemia among Alaska Native children at 14 months after treatment initiation. We hypothesized that 14 months was to early to resolve H. pylori-induced gastric damage. Consequently, we conducted a 40-month follow-up. We enrolled 219 children 7-11 years old who had H. pylori infection (as diagnosed by (13)C-labeled urea breath test) and iron deficiency (serum ferritin level, <22.47 pmol/L) in a controlled, household-randomized trial of the effect of treatment of H. pylori on iron deficiency and anemia (hemoglobin level, <115 g/L). At 40 months, 176 children were evaluated. Forty-four (52%) of 85 children in the intervention group and 53 (58%) of 91 in the control group had iron deficiency (adjusted relative risk [ARR], 0.92 [95% confidence interval {CI}, 0.68-1.26]), versus 4 (5%) and 17(19%), respectively, with both iron deficiency and anemia (ARR, 0.25 [95% CI, 0.09-0.73]). Reinfection occurred among 33 (52%) of 64 children who had cleared their infection. H. pylori-negative children had lower prevalences of iron deficiency (ARR, 0.62 [95% CI, 0.38-1.01]) and iron deficiency and anemia (ARR, 0.22 [95% CI, 0.03-1.50]), compared with H. pylori -positive children. The resolution of H. pylori infection for >14 months modestly reduced the prevalence of iron deficiency and substantially reduced the prevalence of iron deficiency and anemia. H. pylori likely plays a casual role in hematological outcomes for some children.

Antimicrobial Activity of Curcumin against Helicobacter pylori Isolates from India and during Infections in Mice

Treatment failure is a major cause of concern for the Helicobacter pylori-related gastroduodenal diseases like gastritis, peptic ulcer, and gastric cancer. Curcumin, diferuloylmethane from turmeric, has recently been shown to arrest H. pylori growth. The antibacterial activity of curcumin against 65 clinical isolates of H. pylori in vitro and during protection against H. pylori infection in vivo was examined. The MIC of curcumin ranges from 5 microg/ml to 50 microg/ml, showing its effectiveness in inhibiting H. pylori growth in vitro irrespective of the genetic makeup of the strains. The nucleotide sequences of the aroE genes, encoding shikimate dehydrogenase, against which curcumin seems to act as a noncompetitive inhibitor, from H. pylori strains presenting differential curcumin MICs showed that curcumin-mediated growth inhibition of Indian H. pylori strains may not be always dependent on the shikimate pathway. The antimicrobial effect of curcumin in H. pylori-infected C57BL/6 mice and its efficacy in reducing the gastric damage due to infection were examined histologically. Curcumin showed immense therapeutic potential against H. pylori infection as it was highly effective in eradication of H. pylori from infected mice as well as in restoration of H. pylori-induced gastric damage. This study provides novel insights into the therapeutic effect of curcumin against H. pylori infection, suggesting its potential as an alternative therapy, and opens the way for further studies on identification of novel antimicrobial targets of curcumin.

Extracellular pH Modulates Helicobacter pylori-Induced Vacuolation and VacA Toxin Internalization in Human Gastric Epithelial Cells

In this study we investigated whether an acidic extracellular pH may inhibit H. pylori-induced internalization of bacterial virulence factors by gastric epithelium, thus preventing ingestion of potentially dangerous luminal contents and resulting cellular damage. The interaction of H. pylori VacA toxin and ammonia (produced by H. pylori urease) with partly polarized gastric MKN 28 cells in culture was investigated at neutral and moderately acidic pH (6.2, compatible with cell viability) by means of neutral red dye uptake and ultrastructural immunocytochemistry. We found that acidic extracellular pH virtually abolished both VacA-dependent and ammonia-dependent cell vacuolation, as shown by the neutral red test, and caused a 50% decrease in VacA internalization into endosomal vesicles and vacuoles, as assessed by quantitation of immunogold particles. In addition, acidic pH blocked endosomal internalization of H. pylori outer membrane vesicles, a convenient indicator of endocytosis. Our data raise the possibility that suppression of gastric acid may increase H. pylori-induced gastric damage by enhancing epithelial internalization of H. pylori virulence factors through activation of endocytosis. Increased transmembrane diffusion of ammonia could also contribute to this process.

Inhibition of rabbit gastric epithelial restoration by a water extract ofHelicobacter pylori: evidence using a cultured cell model

The detailed mechanism ofH. pylori-induced gastric damage is still unknown. In this study, we showed that a water extract ofH. pylori retarded the epithelial restoration in a cultured rabbit gastric epithelial cell model with the inhibition of both cell migration and proliferation. Although this inhibitory substance has not yet been biochemically characterized, it is different from knownH. pylori associate-cytotoxins and ammonia. From these results, we hypothesize that these bacteria, directly play a role in disturbance of peptic ulcer healing in vivo.

The vacuolating cytotoxin of Helicobacter pylori.

Helicobacter pylori, the causative agent of chronic superficial gastritis and duodenal ulcer disease in humans, produces a unique cytotoxin (VacA) that induces cytoplasmic vacuolation in eukaryotic cells. The structural organization and processing of the vacuolating cytotoxin are characteristic of a family of proteins exemplified by Neisseria gonorrhoeae IgA protease. Although only 50% of H. pylori isolates produce detectable cytotoxin activity in vitro, vacA homologues are present in virtually all isolates. Several families of vacA alleles have been identified, and there is a strong correlation between presence of specific vacA genotypes, cytotoxin activity, and peptic ulceration. Experiments in a mouse model of H. pylori-induced gastric damage indicate that the cytotoxin plays an important role in inducing gastric epithelial necrosis.