Helicobacter Pylori-infected Mongolian Gerbils Research Articles

Apigenin has anti-atrophic gastritis and anti-gastric cancer progression effects in Helicobacter pylori-infected Mongolian gerbils

Ethnopharmacological relevanceApigenin, one of the most common flavonoids, is abundant in celery, parsley, chamomile, passionflower, and other vegetables and fruits. Celery is recognized as a medicinal vegetable in Oriental countries to traditionally treat inflammation, swelling, blood pressure, serum lipid, and toothache. In this study, we investigated apigenin treatment effects on Helicobacter pylori-induced atrophic gastritis and gastric cancer progression in Mongolian gerbils. Materials and methodsFive to eight-week-old Mongolian gerbils were inoculated with Helicobacter pylori for four weeks without (atrophic gastritis group) or with N'-methyl-N'-nitro-N-nitroso-guanidine (MNNG) (gastric cancer group) in drinking water, and were then rested for two weeks. During the 7th–32th (atrophic gastritis group) or the 7th–52th (gastric cancer group) weeks, they were given various doses (0–60mg/kgbw/day) of apigenin. At the end of the 32th (atrophic gastritis group) or the 52th (atrophic gastritis group) week, all Mongolian gerbils were sacrificed using the CO2 asphyxia method. The histological changes of Helicobacter pylori colonization, neutrophil and monocyte infiltrations, and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils were examined using immunohistochemistry stain and Sydney System scoring. ResultsApigenin treatments (30–60mg/kgbw/day) effectively decreased atrophic gastritis (atrophic gastritis group) and dysplasia/gastric cancer (gastric cancer group) rates in Mongolian gerbils. Apigenin treatment (60mg/kgbw/day) significantly decreased Helicobacter pylori colonization and Helicobacter pylori-induced histological changes of neutrophil and monocyte infiltrations and atrophic gastritis in both atrophic gastritis and gastric cancer Mongolian gerbils. ConclusionsApigenin has the remarkable ability to inhibit Helicobacter pylori-induced atrophic gastritis and gastric cancer progression as well as possessing potent anti-gastric cancer activity.

Expression of angiotensin II type 1 and type 2 receptor mRNAs in the gastric mucosa of Helicobacter pylori-infected Mongolian gerbils

The renin-angiotensin system (RAS) plays an important role in normal homeostasis, carcinogenesis-related angiogenesis, and cell proliferation. Helicobacter pylori infection causes infiltration of inflammatory cells into the gastric mucosa and is considered the major cause of gastric cancer. Whether RAS plays a role in H. pylori infection-related gastric diseases remains unclear. We investigated the changes in gastric mucosal angiotensin II type 1 receptor (AT1R) and type 2 receptor (AT2R) mRNA levels throughout the time course of H. pylori infection in Mongolian gerbils. Mongolian gerbils were infected with wild-type H. pylori (for 12 months) or with its isogenic oipA mutant (for 3 months). Gastric mucosal AT1R and AT2R mRNA levels were assessed using real-time reverse transcription-polymerase chain reaction. The gastric mucosal AT1R mRNA level was significantly associated with the severity of inflammatory cell infiltration into the gastric mucosa that reached maximal levels at 12 months after infection in both the antrum and body. Inflammatory cell infiltration scores and AT1R and AT2R mRNA levels were significantly lower in oipA mutant than wild-type infections. Mucosal AT1R and AT2R mRNA expressions in wild-type H. pylori-infected gerbils with gastric ulcers were significantly higher than in those without ulcers (P < 0.01). Gastric mucosal ATR expression gradually increases during the course of H. pylori infection. Up-regulation of the RAS in association with progressive gastric inflammation suggests a potential role of the RAS in gastric carcinogenesis. OipA appears to play a role in AT1R and AT2R expression and the resulting inflammation.

High-Protein Diet Suppresses Corpus Atrophic Gastritis in Helicobacter pylori Infected Mongolian Gerbils

To investigate the effect of a high-protein diet on corpus atrophic gastritis in Helicobacter pylori-infected Mongolian gerbils, H. pylori was administered orally to 5-wk-old Mongolian gerbils; and the animals were then fed a control diet (Group C); a high-fat diet (Group F: 40% fat); a high-protein diet (Group P: 32% protein); or a high-fat, high-protein diet (Group FP: 40% fat, 32% protein) for 50 wk beginning at 7 wk of age. In uninfected animals, the mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). In infected animals, the serum gastrin level was significantly decreased in Group FP and marginally significantly decreased in Group P (P = 0.057) in comparison to Group C. The mucosal thickness of the corpus was significantly greater in Group P and Group FP than in Group C (P < 0.05). Mean inflammation and atrophy scores in the corpus were significantly lower in the high-protein groups (Groups P and FP) than in the control groups (Groups C and F; both inflammation and atrophy: P < 0.05). In conclusion, long-term administration of a high-protein diet suppresses corpus atrophic gastritis in H. pylori-infected Mongolian gerbils.

Celecoxib Inhibits Cdx2 Expression and Prevents Gastric Cancer in Helicobacter pylori-Infected Mongolian Gerbils

Background/Aim: The aim of this study was to see whether administration of celecoxib, a selective COX-2 inhibitor, prior to the appearance of intestinal metaplasia could prevent the development of gastric cancer in Helicobacter pylori-infected Mongolian gerbils. Methods:Fifty-two Mongolian gerbilswere divided into 3 groups and given 5 biweekly doses of N-methyl-N-nitrosourea (MNU; 30 ppm). At week 12, group 2 (n = 20) and group 3 (n = 22) gerbils were then given an injection of H. pylori, while group 1 controls (n = 10) received Brucella broth alone. In addition, 7 weeks after H. pylori inoculation, at week 19, group 3 gerbils also received a 36-week administration course of celecoxib (1,500 ppm) in their diet. The incidence of gastric adenocarcinoma was determined at week 54 by histological analysis. COX-2 and Cdx2 protein expression and COX activity were evaluated for each group. The extent of intestinal metaplasia, Cdx2 and MUC2 expression, and the apoptotic index were evaluated semi-quantitatively by immunohistochemistry. Results: The incidence of gastric adenocarcinoma was: group 1, 0% (0/10); group 2, 65% (13/20), and group 3, 23% (5/22; p < 0.05). Continuous celecoxib administration significantly reduced COX activity and COX-2 protein expression, Cdx2 and MUC2 protein immunoreactivity, and the extent of Alcian blue periodic acid-Schiff-positive intestinal metaplasia in H. pylori-infected gerbils. Celecoxib also induced apoptosis in these gerbils. Significant inhibition of Cdx2 expression in group 3 gerbils was also shown by Western blot analysis. Conclusions: Prior to the first appearance of intestinal metaplasia, timely administration of celecoxib prevents gastric cancer occurrence by disrupting the progression of intestinal metaplasia into gastric carcinoma through its inhibition of Cdx2 expression in MNU-pretreated H. pylori-infected Mongolian gerbils.

Quantitative measurement of nitric oxide and hydrogen peroxide in Helicobacter pylori-infected Mongolian gerbils in vivo

Objective. Peroxynitrite formation, as reflected by nitrotyrosine expression, is low in Helicobacter pylori-infected Mongolian gerbils despite pronounced expression of radical-forming enzymes. The aim of the present study was to investigate in vivo whether H. pylori inhibits either one or both of the nitro- and oxyradical formation pathways. Material and methods. Male Mongolian gerbils were infected with two different H. pylori strains, TN2GF4 and SS1. Six months after inoculation, direct measurement of NO and H2O2 was performed in vivo using electrochemical microsensors positioned in close proximity to the gastric mucosa. Results. In the TN2GF4-infected animals the level of NO was significantly lower than that in controls. No significant difference in NO levels was detected between the SS1-infected group and the controls. H2O2 was significantly increased in the SS1 animals compared with that in controls after 6 months. The H2O2 level in the TN2GF4 group did not differ from that in controls. Conclusions. The results indicate that H. pylori infection is associated with strain-dependent functional inhibition of both the NO and oxyradical formation pathways in the gastric mucosa.

Gastric expression of inducible nitric oxide synthase and myeloperoxidase in relation to nitrotyrosine in Helicobacter pylori-infected Mongolian gerbils

Objective. For obscure reasons Helicobacter pylori infection of the gastric mucosa is maintained despite a pronounced host defence response. The present study elucidates possible H. pylori-related interference in the oxy- and nitro-radical formation pathways. Material and methods. Male Mongolian gerbils were infected with two different H. pylori strains, TN2GF4 and SS1. At 3, 6, 12 or 18 months after inoculation, gastric expressions of myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and nitrotyrosine were assessed by Western blotting. Results. Expression of both iNOS and MPO was markedly up-regulated in the H. pylori-infected animals compared with non-infected controls. The TN2GF4-infected animals initially (at 3 and 6 months) demonstrated pronounced expression of both iNOS and MPO. The SSI-infected animals exhibited a slower onset with significantly increased iNOS after 12 and 18 months. Nitrotyrosine expression was slightly elevated in the infected groups at 3 and 6 months compared with that in the controls. Nitrotyrosine levels then decreased and were no longer significantly different from those of controls (TN2GF4-infected animals) or were lower (SS1-infected animals) than in the controls. Conclusions. The results indicate that peroxynitrite formation as reflected by nitrotyrosine expression is low or even inhibited in chronic H. pylori infection despite pronounced expression of enzymes representing both the oxy- and nitro-radical formation pathways. The results support the theory that H. pylori survival is related to functional inhibition of mucosal enzymatic NO and/or oxy-radical formation.

Gastric and intestinal phenotypes and histogenesis of advanced glandular stomach cancers in carcinogen‐treated, Helicobacter pylori‐infected Mongolian gerbils

The Helicobacter pylori-infected Mongolian gerbil (MG) has been established as an appropriate animal model for studies of stomach cancer development. However, there have hitherto been no data on the phenotypic classification of glandular stomach cancers in H. pylori-infected and non-infected MG. We therefore examined the phenotypes of 50 and six advanced glandular stomach cancers in H. pylori-infected and non-infected MG, respectively, as well as adjacent non-neoplastic mucosa, using several gastrointestinal epithelial phenotypic markers. The lesions were divided phenotypically into 21 gastric, 24 gastric-and-intestinal mixed, four intestinal and one null types, with 90.0% of the lesions harboring gastric elements and 56.0% demonstrating intestinal phenotypic expression in H. pylori-infected MG. All six lesions were classified as gastric type in non-infected MG. There was no clear correlation with the presence of intestinal metaplasia in surrounding mucosa. In conclusion, our data suggest that most advanced adenocarcinomas retain a gastric cellular phenotype in the glandular MG stomach. Thus, it might be proposed that intestinal metaplasia is a paracancerous phenomenon rather than a premalignant condition. H. pylori infection may trigger intestinalization of both stomach cancers and non-neoplastic mucosa.

Inhibitory effect of etodolac, a selective cyclooxygenase-2 inhibitor, on stomach carcinogenesis in Helicobacter pylori-infected Mongolian gerbils

The effect of the selective COX-2 inhibitor, etodolac, on Helicobacter pylori ( Hp)-associated stomach carcinogenesis was investigated in Mongolian gerbils (MGs). Hp-infected MGs were fed for 23 weeks with drinking water containing 10 ppm N-methyl- N-nitrosourea. They were then switched to distilled water and placed on a diet containing 5–30 mg/kg/day etodolac for 30 weeks. We found that etodolac dose-dependently inhibited the development of gastric cancer, and no cancer was detected at a dose of 30 mg/kg/day. Etodolac did not affect the extent of inflammatory cell infiltration or oxidative DNA damage, but it significantly inhibited mucosal cell proliferation and dose-dependently repressed the development of intestinal metaplasia in the stomachs of Hp-infected MGs. These results suggest that COX-2 is a key molecule in inflammation-mediated stomach carcinogenesis and that chemoprevention of stomach cancer should be possible by controlling COX-2 expression or activity.

Expression of leptin in two-layered culture of gastric mucous cells and fibroblasts: effect of Helicobacter pylori attachment.

Our recent histochemical studies have revealed an increase in myofibroblasts and in leptin and its receptor in endothelial cells, and myofibroblasts in Helicobacter pylori-infected human and Mongolian gerbil fundic mucosa. The present study was undertaken to clarify the H. pylori-induced interaction between leptin in cultured gastric surface mucous cells and fibroblasts. GSM06 cells were incubated with an air- liquid interface on a collagen gel layer containing mouse fibroblast cell line L929. Medium containing H. pylori bacilli (ATCC43504) at 10-100 times higher concentration than the GSM06 cells was added from the luminal side and the localization of leptin was observed by immunohistochemistry. The transformation of L929 cells to myofibroblasts was detected by electron microscopy and PR 2D3 immunoreactivity. L929 cells in the control group showed a spindle shape with scarce cytoplasm. In the H. pylori-treated group, L929 cells showed features characteristic of myofibroblasts, and most GSM06 and L929 cells showed leptin immunoreactivity. In contrast, L929 cells incubated with H. pylori alone did not undergo this differentiation. Attachment of H. pylori to surface epithelial cells caused conversion of fibroblasts to myofibroblasts. We suggest that leptin plays a role in this transformation.

Beta-catenin gene alteration in glandular stomach adenocarcinomas in N-methyl-N-nitrosourea-treated and Helicobacter pylori-infected Mongolian gerbils.

The goal of this study was to elucidate whether beta-catenin gene mutations might contribute to glandular stomach carcinogenesis in Helicobacter pylori (H.pylori)-infected Mongolian gerbils. Firstly, exon 3 of gerbil beta-catenin cDNA, a mutation hot spot, was cloned and sequenced and found to have 89.3% homology with the human form and 95.5% with the rat and mouse forms. Peptide sequence in this region was shown to be 100% conserved in these mammals. Then, 45 stomach adenocarcinomas induced with N-methyl-N-nitrosourea (MNU) plus H. pylori infection and 7 induced with MNU alone were examined for beta-catenin expression by immunohistochemistry and for DNA mutations using a combination of microdissection and PCR-single strand conformation polymorphism analysis. One gastric cancer in the MNU + H. pylori group (2.2%) displayed nuclear (N) beta-catenin localization, 3 (6.7%) showed cytoplasmic (C) distribution in local regions, and 41 (91.1%) demonstrated cell membrane (M) localization. Tumors induced by MNU alone showed only membranous beta-catenin localization (7/7). Analysis of exon 3 of the beta-catenin gene dem-onstrated all tumors with membrane or cytoplasmic staining as well as surrounding normal mucosa (S) to feature wild-type beta-catenin. In contrast, the lesion with nuclear staining had a missense mutation at codon 34 [GAC (Gly) --> GAA (Glu)] in exon 3 (1/1 = 100%, N vs. M, P < 0.05; and N vs. S, P < 0.05). In conclusion, these results suggest that beta-catenin may not be a frequent target for mutation in stomach carcinogenesis in MNU + H. pylori-treated gerbils.

Effect of duodenogastric reflux on N-methyl-N'-nitro-N-nitrosoguanidine-induced glandular stomach tumorigenesis in Helicobacter pylori-infected Mongolian gerbils

Both Helicobacter pylori (Hp) and bile acids are gastric carcinogens. An experimental model of duodenogastric reflux in Mongolian gerbils was developed and was used to study the effects of Hp infection and duodenogastric reflux on N-methyl-N'-nitro-N-nitrosoguanidine (MNNG)-induced glandular stomach tumorigenesis independently and synergistically. Male Mongolian gerbils underwent both inoculation with Hp, and had duodenogastric reflux (DR) induced, or neither, followed by MNNG administration. Animals were sacrificed at week 40, and histopathological examination of their excised stomachs and serological investigation were performed. Glandular stomach adenocarcinomas were observed in animals that underwent Hp inoculation and/or induction of DR after MNNG administration, and glandular stomach adenomas were found in animals inoculated with Hp after MNNG administration. The incidence of glandular stomach tumors was significantly higher in animals inoculated with Hp after MNNG administration and in animals undergoing combined Hp inoculation, DR induction and MNNG administration than in animals only administered MNNG. These findings indicate that Hp infection has a stronger tumorigenic effect than the exposure to duodenal contents, and duodenal contents may attenuate the effect of Hp on glandular stomach tumorigenesis.

Interaction of leptin with gastric myofibroblast transdifferentiation in Helicobacter pylori-infected Mongolian gerbils: the effect of rebamipide.

Our recent histochemical studies have revealed the marked increase of myofibroblasts in the Helicobacter pylori-infected Mongolian gerbil fundic mucosa, while the mediators, which facilitate the conversion of fibroblasts to the myofibroblasts have remained unknown. The present study was undertaken to clarify the alteration of leptin in the control and H. pylori-infected Mongolian gerbil stomach. The effector sites of rebamipide were also investigated in relation to leptin. The localization of leptin was investigated by the indirect immunofluorescence. Plasma leptin levels were determined by ELISA method. The localization of 3H-rebamipide binding sites was investigated by autoradiography. Serum leptin content in H. pylori-infected Mongolian gerbils was significantly increased. The presence of leptin immunoreactivity was recognized in the endothelial cells of the microcirculatory network and very weakly in the glandular cells in the control group, while in the H. pylori-infected group leptin was markedly recognized in the mesenchymal cells. Rebamipide bound to the fibroblasts and surface mucous cells and decreased the leptin immunoreactivity in the gastric mucosa. Leptin was mostly found in the mesenchymal cells. Rebamipide administration brought about the decrease of leptin in the gastric mucosaof the H. pylori-infected gerbils.

Long-term Treatment with Sterigmatocystin, a Fungus Toxin, Enhances the Development of Intestinal Metaplasia of Gastric Mucosa in Helicobacter pylori-infected Mongolian Gerbils

Background: Helicobacter pylori is a human gastric carcinogen. Sterigmatocystin (ST), a fungus toxin, is a risk factor of gastric cancer. Cytotoxin-vacuolation toxin A (VacA) present in supernatants of H. pylori suspensions can cause gastritis and ulcer. The aim of this study was to examine the effects of H. pylori, ST and VacA in Mongolian gerbils. Methods: Male Mongolian gerbils (n = 196) were treated with H. pylori supernatants (10 ml/1000 mg) mixed with diet or inoculated intragastrically with H. pylori alone or with ST (100 or 1000 ppb), and then killed 27 months later. Gastric tissue sections were stained with haematoxylin and eosin (H&E), periodic acid-Schiff (PAS), Alcian blue (AB, pH 2.5) and with immunostaining for PCNA and p53 expression. Results: In H. pylori-infected gerbils, the normal mucosa was replaced by hyperplastic epithelium. Severe gastritis, cystic dilatation of gastric glands, hyperplastic polyps and intestinal metaplasia were observed. In H. pylori + ST (1000 ppb) gerbils, intestinal metaplasia was significantly more frequent than in H. pylori alone animals. No pathological changes were observed in the H. pylori supernatant group. Osseous metaplasia was observed in the H. pylori + ST (100 ppb) group. Serum gastrin levels of the H. pylori + ST (1000 ppb) group were significantly higher than those of the other groups. PCNA labelling index and p53 index of infected gerbils were significantly higher than those of uninfected groups. Conclusion: H. pylori causes gastritis, ulcer and intestinal metaplasia. ST enhances the development of intestinal metaplasia and increases gastrin levels in H. pylori-infected Mongolian gerbils.

Role of elastase and active oxygen species in gastric mucosal injury induced by aspirin administration in Helicobacter pylori-infected Mongolian gerbils.

H. pylori infection potentiates aspirin-induced gastric mucosal injury by mechanisms that include accumulation of activated neutrophils. To determine the role of elastase and active oxygen species (AOS) produced by activated neutrophils in the gastric mucosal injury induced by administration of acidified aspirin to H. pylori-infected Mongolian gerbils. H. pylori ATCC43504 culture broth was administered by oral gavage to male Mongolian gerbils at 7 weeks of age. After 4 weeks, acidified aspirin (400 mg/kg) was administered orally, and 3 h later, the total area of gastric erosions, myeloperoxidase (MPO) activity (an index of neutrophil accumulation), thiobarbituric acid-reactive substances (TBARS, an index of lipid peroxidation), and KC/GRO (a chemo-attractive cytokine in rodents) were measured in gastric mucosa. To determine the role of elastase or AOS derived from neutrophils in these circumstances, ONO-5046 (an elastase inhibitor), a combination of superoxide dismutase (SOD) and catalase (scavengers of AOS), and polaprezinc (an anti-ulcer agent with anti-inflammatory effects) were administered before aspirin. ONO-5046 inhibited the increase in gastric erosions and mucosal TBARS induced by administration of aspirin to H. pylori-infected gerbils, but not the increases in MPO activity or KC/GRO contents. A combination of SOD and catalase or polaprezinc significantly reduced gastric erosions, TBARS concentrations, MPO activity and KC/GRO concentration. These results suggest that neutrophil-derived-elastase and -oxidants play an important role in the gastric mucosal injury induced by administration of aspirin to H. pylori-infected gerbils.

Early gastric mucosal lesions in helicobacter pylori infected mongolian gerbils

Early gastric mucosal lesions in helicobacter pylori infected mongolian gerbils

Pharmacological study on the pathological changes of the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils

Helicobacter pylori (H. pylori) infection has been recognized to be a causal factor of gastritis, ulcers and gastric cancer in man. Using Mongolian gerbils (M. gerbils), which are suitable for an H. pylori infection animal model, we examined 1) how H. pylori infection, indomethacin and their combination affects the healing of gastric ulcers and whether or not such factors provoke a relapse of healed acetic acid ulcers; and 2) whether or not eradication of the bacteria with drugs at specified times after infection prevents the development of mucosal changes, including gastric adenocarcinoma. 1) H. pylori infection significantly delayed ulcer healing 4 weeks following infection. Indomethacin treatment showed a tendency to delay ulcer healing. Ulcer healing in H. pylori-infected M. gerbils was significantly delayed by indomethacin. H. pylori infection resulted in a relapse of healed ulcers from 1 to 6 months after infection, with a gradual increase in size. Omeprazole markedly prevented the ulcer relapse caused by H. pylori infection. 2) Four or 8 months after H. pylori inoculation, eradication was performed by concurrent treatment with omeprazole + clarithromycin. Immediately after treatment ended in both the 5 and 9 month groups, it was verified that H. pylori were completely eradicated. Autopsy performed 18 months after H. pylori inoculation revealed gastric hyperplastic polyps with erosive lesions and ulcers that were grossly visible; and atrophic gastritis, intestinal metaplasia, carcinoids, and adenocarcinomas were histologically observed in the non-treated control group. In animals eradicated after 4 months and autopsied after 18 months, however, such mucosal changes were not observed. In contrast, intestinal metaplasia and mucosal atrophy was observed in animals eradicated after 8 months and autopsied after 18 months. It was concluded that 1) H. pylori infection delayed the healing of preexisting gastric ulcers and resulted in the relapse of healed ulcers, yet indomethacin had little or no effect on ulcer healing or relapse; and 2) early eradication of H. pylori infection with drug therapy can prevent severe gastric mucosal changes, to include adenocarcinomas, in M gerbils.

Nonsteroidal anti-inflammatory drug-induced acute gastric injury in Helicobacter pylori gastritis in Mongolian gerbils

We examined the acute ulcerogenic effects of indomethacin and N-(2,cyclohexyloxy-4-nitrophenyl)methane sulfonamide (NS-398) on the gastric mucosa in Helicobacter pylori-infected Mongolian gerbils. H. pylori infection for 4 and 12 weeks caused moderate and severe gastritis, respectively, with cyclooxygenase-2 expression and an increase in prostaglandin E 2 production. In normal animals, gastric injury was caused by indomethacin, but not by NS-398. At 4 weeks infection, gastric lesions were synergistically aggravated by indomethacin, and NS-398 at high doses. However, at 12 weeks, the synergistic effects of indomethacin and NS-398 with H. pylori were not observed. Indomethacin and NS-398 at high doses inhibited prostaglandin E 2 production in both normal and the infected mucosa. NS-398 at low dose reduced only the H. pylori-increased prostaglandin production. These results suggest that nonsteroidal anti-inflammatory drugs (NSAIDs) synergistically aggravate gastric lesions in moderate H. pylori gastritis, but not in severe gastritis. Cyclooxygenase-2 inhibition only might not induce acute gastric injury in H. pylori gastritis.

COX-2 protects gastric mucosa against damage caused by nsaid in Helicobacter pylori-infected mongolian gerbils

COX-2 protects gastric mucosa against damage caused by nsaid in Helicobacter pylori-infected mongolian gerbils

S6–4 - Effects of NSAIDs in Helicobacter pylori-infected Mongolian gerbils

S6–4 - Effects of NSAIDs in Helicobacter pylori-infected Mongolian gerbils

Synthesis and structure-activity relationships of 7-(2-aminoalkyl)morpholinoquinolones as anti-Helicobacter pylori agents.

A series of the titled compounds was synthesized and tested for anti-Helicobacter pylori activities. We discovered Y-34867 having the most potent activity against Helicobacter pylori among the quinolones tested along with high photostability. Furthermore, Y-34867 showed an excellent therapeutic effect in the experimental Helicobacter pylori infected Mongolian gerbil model.